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In this article, which is part of the Currents in One Health series, principles of immunotherapeutics are discussed and their clinical exploration in dogs reviewed with emphasis on their translatability for improving treatment of commonly diagnosed cancers. With increasing longevity and sustained quality of life in pet dogs through dietary, environmental awareness, and preventative medical practices, the geriatric pet population has continued to steadily grow and, consequently, so have age-related pathologies. Not surprisingly, cancer is the most common cause of mortality in elderly dogs, accounting for 1 in 4 deaths in dogs > 10 years of age. Importantly, some cancer types that arise spontaneously in pet dogs are similar to cancers afflicting people. The shared clinical and biological behaviors of certain cancers observed in pet dogs and people underscore the opportunity to leverage comparative oncology studies, which can accelerate the validation and clinical implementation of innovative therapies that can benefit pet dogs and ultimately guide these strategies toward clinical practice in people too. In the era of immunotherapy, the inclusion of pet dogs that develop cancers under an intact immune system affords a unique and high-value opportunity to study the evolving nature of cancers shaped by immunosurveillance pressures. Complementing these discovery efforts and through a comparative oncology approach, the exploration and clinical validation of novel immunotherapeutic strategies in pet dogs can be foundational for defining the safety and immune-activating potential of new anticancer immune approaches that hold promise to transform cancer treatment in both pets and people alike.

The blood-brain barrier and knowledge gaps in tumor biology remain significant obstacles to the development of effective treatments for brain tumors. The identification of shared molecular and genetic pathways that contribute to tumorigenesis in both dogs and people has been key to the discovery and translation of targeted pharmacologic and biologic therapies. Treatment approaches often utilize targeted or multifunctional antitumor agents, such as nanocarriers, molecularly targeted agents, immunotherapeutics, and oncolytic viruses in combination with alternative therapeutic delivery strategies. The article discusses about various treatments albeit none of the treatments discussed here are widely available or approved for clinical use., Competing Interests: Disclosure J.H. Rossmeisl holds patents and has patents pending on QUAD compound targeted and oncolytic viral therapeutics for cancer and is an advisory board member with Zoetis., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Mastitis is an inflammatory condition that affects dairy cow's mammary glands. Traditional treatment approaches with antibiotics are increasingly leading to challenging scenarios such as antimicrobial resistance. In order to mitigate the unwanted side effects of antibiotics, alternative strategies such as those that harness the host immune system response, also known as immunotherapy, have been implemented. Immunotherapy approaches to treat bovine mastitis aims to enhance the cow's immune response against pathogens by promoting pathogen clearance, and facilitating tissue repair. Various studies have demonstrated the potential of immunotherapy for reducing the incidence, duration and severity of mastitis. Nevertheless, majority of reported therapies are lacking in specificity hampering their broad application to treat mastitis. Meanwhile, advancements in mastitis immunotherapy hold great promise for the dairy industry, with potential to provide effective and sustainable alternatives to traditional antibiotic-based approaches. This review synthesizes immunotherapy strategies, their current understanding and potential future perspectives. The future perspectives should focus on the development of precision immunotherapies tailored to address individual pathogens/group of pathogens, development of combination therapies to address antimicrobial resistance, and the integration of nano- and omics technologies. By addressing research gaps, the field of mastitis immunotherapy can make significant strides in the control, treatment and prevention of mastitis, ultimately benefiting both animal and human health/welfare, and environment health.

In this study, the immunohistochemical expression of programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1), which could facilitate a novel approach to immunotherapy for feline injection site sarcomas (FISSs), was investigated. Treatment strategies based on the suppression of this pathway are possible for tumours expressing PD-1/PD-L1. In this context, FISSs were histologically classified, the grade of sarcoma and the intensity of lymphocyte infiltration determined and PD-1 and PD-L1 expression evaluated in tumours of different grade. Tumours were immunolabelled for vimentin, S100, smooth muscle actin and sarcomeric actin. Fibrosarcoma was diagnosed in eight cases, undifferentiated sarcoma in one case, liposarcoma in one case and rhabdomyosarcoma in one case. PD-1 expression was found mainly in lymphoid infiltrations and macrophage-like cells, while PD-L1 was found primarily in tumour cells and infiltrated macrophage-like cells. By Pearson correlation analysis, tumour differentiation was found to have a moderate correlation with PD-1 (P <0.05) and a high correlation with PD-L1 (P <0.01). Tumour grade had a low correlation with PD-1 and a moderate correlation with PD-L1 (P >0.05). A moderate correlation was also detected between PD-1 and PD-L1 (P <0.05). It was concluded that the increased expression of PD-1 and PD-L1 may be associated with poor tumour differentiation and, therefore, poor prognosis in FISS., Competing Interests: Declaration of competing interests The authors declared no conflicts of interest in relation to the research, authorship and publication of this article., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The enhanced understanding of immunology experienced over the last 5 decades afforded through the tools of molecular biology has recently translated into cancer immunotherapy becoming one of the most exciting and rapidly expanding fields. Human cancer immunotherapy is now recognized as one of the pillars of treatment alongside surgery, radiation, and chemotherapy. The field of veterinary cancer immunotherapy has also rapidly advanced in the last decade with a handful of commercially available products and a plethora of investigational cancer immunotherapies, which will hopefully expand our veterinary oncology treatment toolkit over time., Competing Interests: Disclosure Dr P.J. Bergman is a co-inventor on patent US7556805B2 and was the veterinary principal investigator for the canine melanoma vaccine Oncept which received USDA-CVB conditional licensure in 2007 and full licensure in December of 2009. He also receives a minority royalty stream payment., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The ability to genetically redirect the antigenic specificity of T cells using chimeric antigen receptors (CAR) has led to unprecedented durable clinical remissions in human patients with relapsed/refractory hematological malignancies. This remarkable advance in successful immune cell engineering has now led to investigations into the application of CAR-T-cell technology to treat nonmalignant diseases. The use of CAR-T cells to target and eliminate specific cell subsets involved in the pathogenesis of autoimmunity, fibrosis, senescence, and infectious disease represents a new direction for adoptive cell therapies. While the use of CAR-T cells for nonmalignant disease is still in its infancy, early reports of dramatic clinical responses to CAR-T cells targeting CD19+ B cells in patients with severe autoimmune disease raise the possibility that this approach could lead to durable remissions, eliminating the need for ongoing conventional immunosuppressive therapies. Excitingly, nonmalignant disease processes that may be addressed by CAR-T-cell therapy in humans also occur in our canine populations. Given that technologies for developing canine CAR constructs are now available, robust protocols have been described for generating canine CAR-T cells, and experience is being gathered with their clinical use in oncology, it is anticipated that CAR-T cells will soon enter the veterinary clinics for the treatment of debilitating nonmalignant diseases. Here, we provide a broad overview of CAR-T-cell therapies for nonmalignant diseases and extrapolate these advances into the veterinary space, highlighting areas in which canine CAR-T cells are poised to enter the clinics for the treatment of nonmalignant disease.

Background: Allermmune HDM (Zenoaq) is a recombinant Dermatophagoides farinae 2 (Der f 2) pullulan-based immunotherapy vaccine whose efficacy on house dust mite allergic dogs has been demonstrated. There is no published information on its use in cats., Objectives: The objective of the study was to evaluate the safety and short-term effects of Allermmune HDM in Dermatophagoides farinae (Df)-sensitised cats., Materials and Methods: Eleven cats diagnosed with atopic skin syndrome received Allermmune weekly for six weeks then monthly for three months (total duration 18 weeks). On Weeks 0, 6 and 18 clinical lesions were assessed by the Feline Dermatitis Extent and Severity Index (FEDESI); owners assessed pruritus with a 10-cm Visual Analog Scale (pVAS). Concurrent medication use was recorded. The allergen-specific immunoglobulin (Ig)E were measured before study inclusion with a commercial serological assay., Results: There were no evident adverse effects. FEDESI and pVAS improved significantly after six weeks (p = 0.001 and p = 0.01, respectively). The pretreatment Df-specific IgE levels were significantly higher in the cats with improved clinical scores than in the cats with no clinical score change (p = 0.009)., Conclusions and Clinical Relevance: Allermmune HDM may be safe in cats and has the potential to alleviate signs of atopic skin syndrome. Allergen-specific IgE levels may represent an efficacy marker. Controlled studies of longer duration and larger sample size are worth pursuing., (© 2023 ESVD and ACVD.)

Background: Hymenoptera envenomation occurs frequently in people and dogs and can trigger anaphylaxis. Venom immunotherapy (VIT) is the only preventive treatment for Hymenoptera hypersensitivity and is indicated for people with severe adverse reactions to insect stings. Rush VIT is an accelerated VIT protocol in people. This has not been reported in dogs., Objectives: The objective of the study was to evaluate the safety of modified rush VIT., Animals: Twenty client-owned dogs with Hymenoptera hypersensitivity based on a history of adverse reactions to Hymenoptera envenomation and a positive intradermal test to honey bee and/or paper wasp venom., Materials and Methods: Dogs received incremental doses of venom via subcutaneous injection one day per week for three consecutive weeks until the maintenance dose was achieved. Vital signs were recorded every 30 min prior to venom administration. Adverse reactions were categorised as localised or grade I-IV systemic reactions., Results: Nineteen of 20 dogs (95%) completed rush VIT. One dog experienced a grade III systemic adverse reaction and was withdrawn from the study. No adverse reactions occurred in 10 of 20 dogs (50%). Localised and grade I-II systemic reactions occurred in nine of 20 dogs (45%), including nausea (n = 5), injection site pruritus (n = 3) and diarrhoea and lethargy (n = 1)., Conclusions and Clinical Relevance: Modified rush VIT in dogs was well-tolerated and should be considered for dogs with Hymenoptera hypersensitivity. Larger studies are needed to evaluate the efficacy of VIT in dogs for preventing hypersensitivity reactions to insect stings., (© 2023 The Authors. Veterinary Dermatology published by John Wiley & Sons Ltd on behalf of ESVD and ACVD.)

Background: The duration of the induction phase of allergen-specific immunotherapy conventionally is a period of several weeks, during which the volume of an allergen solution, administered by injection, is gradually increased until the maintenance dose is reached. In rush immunotherapy (RIT), the induction period is abbreviated to achieve a faster improvement in clinical signs of atopic dermatitis (AD) compared to conventional immunotherapy., Objective: The aim of this retrospective study was to evaluate the safety of RIT in 230 dogs with AD and report any adverse effects (AE)., Animals: Two hundred thirty client-owned dogs., Materials and Methods: Medical records of dogs receiving RIT between 2012 and 2021 were analysed and observed AE were investigated. All dogs underwent RIT following a protocol of subcutaneous allergen extract injections, given hourly with an incrementally increasing volume from 0.1 to 1.0 mL., Results: Adverse effects were documented in 6 of 230 (2.6%) dogs. Five of these dogs (2.2%) showed mild gastrointestinal signs (1 of 5 vomiting, 4 of 5 diarrhoea) and one patient an increase in body temperature by 1.5°C. These occurred at different stages of the RIT protocol. All AE were graded as mild and self-limiting., Conclusions and Clinical Relevance: Based on these data, supervised RIT in dogs appears to be a safe procedure to achieve the maintenance dose of allergen immunotherapy earlier with infrequent and mild AE., (© 2023 The Authors. Veterinary Dermatology published by John Wiley & Sons Ltd on behalf of ESVD and ACVD.)

Recent studies have highlighted a key role played by the sympathetic nervous system (SNS) and adrenergic stress in mediating immune suppression associated with chronic inflammation in cancer and other diseases. The connection between chronic SNS activation, adrenergic stress and immune suppression is linked in part to the ability of catecholamines to stimulate the bone marrow release and differentiation of myeloid-derived suppressor cells (MDSC). Rodent model studies have revealed an important role for β-adrenergic receptor signalling in suppression of cancer immunity in mice subjected to chronic stresses, including thermal stress. Importantly, therapeutic blockade of beta-adrenergic responses by drugs such as propranolol can partially reverse the generation and differentiation of MDSC, and partly restore tumour immunity. Clinical trials in both humans and dogs with cancer have demonstrated that propranolol blockade can improve responses to radiation therapy, cancer vaccines and immune checkpoint inhibitors. Thus, the SNS stress response has become an important new target to relieve immune suppression in cancer and other chronic inflammatory conditions., (© 2023 The Authors. Veterinary and Comparative Oncology published by John Wiley & Sons Ltd.)

Objective: The anti-GnRH immunotherapeutic product Improvest was administered to intact male large flying foxes (Pteropus vampyrus) under managed care for androgen mitigation, leading to a decrease in agonistic behaviors, falls, and injuries from conspecific attention., Animals: 12 males were included in this study., Procedures: Eleven bats received subcutaneous (SC) Improvest interscapular, and 1 animal received Improvest SC in its leg. Assessments included clinical presentation, treatment, behavior, and urine and fecal glucocorticoid metabolites and testosterone (T5) concentrations., Results: Eleven of the 12 bats developed reactions, which included facial edema, localized irritation, swelling of the head and neck, and pruritus with varying degrees of skin ulceration and subsequent necrosis. Three of the animals required extensive treatments, and the 1 animal who received the injection in its leg was unaffected. Posttreatment, fecal glucocorticoid metabolite and/or T5 values were at or below the nonbreeding season baseline for 3 successive breeding seasons, and there was a reduction in agonistic interactions, falls, and injuries., Clinical Relevance: A behavioral characteristic of this species is to focus on areas of irritation that exacerbated the extent of the skin wounds. Some cases required medical, surgical, and behavioral intervention. Large flying foxes may be particularly sensitive to this immunotherapeutic when given subcutaneously in the interscapular region. Despite this reaction, the positive long-term effects on behavior and multiyear reduction of hormones suggest that the use of this immunotherapeutic warrants further investigation, although the results should be taken into consideration with other factors such as handling, treatments, chronicity of lesions.

Human and canine sarcomas are difficult to treat soft tissue malignancies with an urgent need for new improved therapeutic options. Local recurrence rates for humans are between 10%-30%, and 30%-40% develop metastases. Outcomes for dogs with sarcoma vary with grade but can be similar. Pet dogs share the human environment and represent human cancer with genetic variation in hosts and tumours. We asked if our murine studies using genetically identical mice and cloned tumour cells were translatable to larger, genetically diverse domestic dogs with naturally occurring tumours, to (i) develop a canine cancer therapeutic, and (ii) to use as a translational pathway to humans. Our murine studies showed that intra-tumoral delivery of interleukin-2 (IL-2) plus an agonist anti-CD40 antibody (Ab) induces long-term curative responses ranging from 30% to 100%, depending on tumour type. We developed an agonist anti-canine-CD40 Ab and conducted a phase I dose finding/toxicology 3 + 3 clinical trial in dogs (n = 27) with soft tissue sarcomas on account of suitability for intratumoral injection and straightforward monitoring. Dogs were treated with IL-2 plus anti-CD40 antibody for 2 weeks. Three dose levels induced tumour regression with minimal side effects, measured by monitoring, haematological and biochemical assays. Importantly, our mouse and canine studies provide encouraging fundamental proof-of-concept data upon which we can develop veterinary and human immunotherapeutic strategies., (© 2022 Selvax Pty Ltd. Veterinary and Comparative Oncology published by John Wiley & Sons Ltd.)

Background: Canine atopic dermatitis (cAD) is an allergic skin disease affecting approximately 10% of dogs. allergen-specific immunotherapy (ASIT) is currently the only treatment option able to induce tolerance to the causative allergens., Objective: To retrospectively establish the efficacy of ASIT in atopic dogs., Animals: Client-owned (n  = 664) dogs with cAD presented between 2008 and 2018 to two dermatology referral clinics., Materials and Methods: Clinical records of atopic dogs were reviewed to obtain information including the results of the intradermal skin test and/or allergen-specific immunoglobulin (Ig)E serological results, the allergens included in the ASIT, concurrent symptomatic medications, and ASIT efficacy after at least 9 months., Results: Excellent (ASIT alone controlled clinical signs), good (≥50% reduction of clinical signs) and poor (<50% improvement) responses were seen in 31.5%, 28.5% and 40.1% of the dogs, respectively. No significant differences in efficacy were associated with breed, sex, age at initiation of ASIT, type of allergens in ASIT, and between clinics. Dogs re-examined regularly responded significantly better to ASIT than dogs that did not (>50% improvement in 69.3% and 55.4% of the dogs, respectively). Dogs treated with ASIT and concomitant systemic glucocorticoids showed a significantly poorer response (success rate of >50% improvement of 38.5%)., Conclusions and Clinical Importance: In 59.9% of atopic dogs, subcutaneous ASIT can improve clinical signs by ≥50%. The beneficial effect of ASIT is higher if dogs are re-examined regularly and if systemic long-term corticosteroids are avoided, at least during the first 9 months of ASIT., (© 2022 The Authors. Veterinary Dermatology published by John Wiley & Sons Ltd on behalf of ESVD and ACVD.)

Background: Human studies suggest that the cytokines, interleukin 10 (IL-10) and transforming growth factor-beta 1 (TGF-ß1) may play an important role in allergen-specific immunotherapy (ASIT). However, there is little known about the function of these cytokines in atopic dogs. This study compared the plasma levels of IL-10 and TGF-ß1 in atopic and control dogs and investigated their changes during different ASIT approaches., Methods: A total of 54 atopic and 32 control dogs were included. Immunotherapy was performed in 30 atopic dogs. The dogs undergoing immunotherapy were allocated to four groups of different ASIT approaches (namely subcutaneous, intralymphatic, sublingual ASIT and subcutaneous ASIT with recombinant allergens). Blood samples were collected at four timepoints throughout the one year of ASIT. Canine atopic dermatitis extent and severity index, pruritus visual analogue scale and medication score were recorded at each timepoint. Commercially available ELISA kits were used to quantify IL-10 and TGF-ß1 in plasma., Results: There was no significant difference in IL-10 and TGF-ß1 between atopic and control dogs. The IL-10 levels were significantly increased in the intralymphatic group at the end of the study. No significant differences were found in the other groups for both IL-10 and TGF-ß1., Conclusion: The findings of this work suggest that IL-10 and TGF-ß1 cannot be used to monitor the course of the disease during ASIT., (© 2021 The Authors. Veterinary Record published by John Wiley & Sons Ltd on behalf of British Veterinary Association.)

Background: Allergen-specific immunotherapy (ASIT) is reported to have a success rate of 50-70% when given for up to 12 months to dogs with atopic dermatitis (AD). How soon ASIT is clinically effective is unclear., Objectives: To compare the efficacy rate (ER) and time-to-efficacy (TTE) of various types of subcutaneous immunotherapy (SCIT) administered using conventional dosing regimens using the methodology of a critically appraised topic., Methods and Materials: Three databases were searched to extract information on the ER and TTE of SCIT in dogs with AD. Herein, "efficacy" was defined as a ≥50% reduction in pruritus and/or skin lesions, and the TTE as the time needed to achieve such a reduction., Results: We selected 12 publications including 194 dogs. The ER was significantly higher with the polymerised allergoids coupled with nonoxidized mannan than for the "classic" aqueous and alum-precipitated SCIT types. A TTE of three months or shorter was seen in a significantly higher proportion of dogs receiving mannan-couple allergoids, pullulan-conjugated Der f 2 or tyrosine-adjuvanted than aqueous or alum-precipitated SCIT; with the latter two formulations, the TTE might be nine months or longer in ≤20% of atopic dogs., Conclusions and Clinical Relevance: In spite of the low number of articles available for review and small number of enrolled dogs, novel SCIT regimens appear to have a faster - and possibly higher - efficacy than the currently available aqueous or alum-precipitated formulations. A standardisation of outcome measures for ASIT clearly is needed to allow a more meaningful comparison between SCIT types., (© 2021 ESVD and ACVD.)

Background: Limited information is known on adverse events and efficacy associated with venomous insect immunotherapy (VIT) in canine patients., Objectives: To assess adverse events associated with VIT and perceived efficacy of VIT., Animals: Records from 82 client-owned animals which received VIT were assessed., Methods and Materials: A retrospective review of records from 2002 to 2020. Clinical history, adverse events during therapy and observations following field stings were collected from all records. Patients were grouped into reactors and nonreactors based on whether or not an adverse event had occurred during therapy. Records were evaluated to determine if a field sting had occurred and the severity of the reaction was compared to pretreatment reaction., Results: Of 82 patients that were identified, 26 experienced a minimum of one adverse event. No deaths or severe anaphylactic reactions were reported. The most common adverse event was gastrointestinal upset. The overall reaction rate per injection was 2.8%. Only variation in sensitisation level (the minimum concentration of venom which elicited a positive intradermal reaction) was significantly different between groups (P = 0.014). Forty-one field challenges in 26 patients were documented. Therapy reduced the severity of reactions in 87.8% of challenges. No deaths were reported., Conclusion: Venom immunotherapy appears to be a safe and efficacious treatment for prevention of anaphylaxis due to insect stings in canine patients., (© 2021 ESVD and ACVD.)

Cancer immunotherapy is a novel cancer treatment for canine tumors. Indoleamine 2,3-dioxygenase 1 (IDO1) is overexpressed in some human tumors and inhibits antitumor immunity. In this study, we comprehensively evaluated expression pattern of IDO1 and the nature of IDO1-expressing cells in canine normal and tumor tissues. In normal tissue samples, IDO1 expression was detected only in the lymph nodes, spleen, tonsil tissues, and colon tissues. In contrast, IDO1-positive tumor cells were observed in several tumor tissue types. This is the first study to evaluate IDO1 expression in canine normal and tumor tissues, and the results suggest that IDO1 is a promising target for novel cancer immunotherapy in dogs with tumors.

Background: Feline atopic syndrome (FAS) is a common disease. Single intradermal injections of heat-killed actinomycetales have shown beneficial effects in canine allergies., Hypothesis/objective: To evaluate the clinical effects of heat-killed actinomycetales [Gordonia bronchialis (GB) and Rodococcus coprophilus (RC)], alone or in combination, in FAS., Methods and Materials: Privately owned cats with a diagnosis of FAS were assigned randomly in three treatment groups (GB, RC and GB/RC combination) or placebo. Five intradermal injections were performed over a one year period. At each visit [Day (D)0, D20, D40, D60, D90, D180 and D365], clinical signs, global owner assessment score, use of rescue medications, clinical adverse effects, skin hydration and cutaneous pH were assessed., Results: Seventeen cats were enrolled. When compared to the placebo group and improvement in treatment GB was sustained from D90. When compared with D0 significant improvement in the GB group was seen from D60. Over one year, a complete remission of the clinical signs was seen in 30-67% of cats in the treatment groups. A reduction in the pruritus score was seen for RC after 365 days of treatment (P = 0.04). Differences in the other variables were not seen., Conclusions and Clinical Importance: The use of multiple intradermal injections of heat-killed GB shows promise as effective and well-tolerated treatment for FAS. Because of the low cost and the lack of adverse effects, GB could be a beneficial treatment option for FAS. A larger study is needed to confirm these data and to evaluate the immunological changes occurring in the treated cats., (© 2021 ESVD and ACVD.)

This case series describes the diagnosis of allergic dermatitis and management with allergen-specific immunotherapy (ASIT) based on intradermal allergy testing (IDAT) and adjunctive medical therapy in six pteropid bats; five large flying foxes ( Pteropus vampyrus ); and one variable flying fox ( Pteropus hypomelanus ). The cases ranged from 2 to 15 yr of age at the time of presentation. Clinical signs varied between individuals and included moist ulcerative cutaneous lesions in nonhaired skin, blepharoconjunctivitis, alopecia, and pruritus. All bats underwent IDAT under general anesthesia, and reactive allergens included a mixture of grasses, trees, weeds, and biting insects. Three of the six cases (50%) had reformulation of the ASIT before control of clinical signs was seen, and two bats were treated with the addition of oclacitinib (Apoquel). Severe adverse effects were not identified; however, one bat had self-limiting swelling at the immunotherapy injection site. All six cases showed improvement of clinical signs and perceived comfort level, including in subsequent allergy seasons.

Adoptive cell transfer (ACT) is a burgeoning therapeutic modality within human immuno-oncology. Novel approaches towards ACT are being developed in the pre-clinical setting faster than they can be evaluated in human clinical trials. Many of the therapeutic approaches used in human medicine have already been evaluated to some degree in canine patients. While this form of immunotherapy in veterinary medicine is still in its infancy, as these approaches develop, canine ACT will become a tool for both the veterinary oncologist and the translational researcher. This review details canine ACT trials to date, with attention given to the precedents provided by human oncology., (© 2021 John Wiley & Sons Ltd.)

Background: Canine atopic dermatitis (cAD) is a pruritic allergic skin disease most often caused by Dermatophagoides farinae. Differences in the sensitization profile to D. farinae have been reported between people and dogs. However, allergic dogs traditionally have been treated with extracts intended for human immunotherapy., Hypothesis/objectives: To develop a specific allergen immunotherapy for veterinary practice enriched in canine major allergens and to demonstrate its in vitro efficacy., Animals: Twenty privately owned dogs, clinically diagnosed with cAD, and three healthy dogs., Methods and Materials: A veterinary D. farinae allergen extract was manufactured and characterized compared to D. farinae extract used for human immunotherapy. The protein profile was analysed by SDS-PAGE and size exclusion chromatography and Der f 15 and Der f 18 allergens quantified by mass spectrometry. The allergenic profile was studied by immunoblot and the biological potency by enzyme-linked immunosorbent assay-inhibition assays. The extract's capacity to induce cytokine production [interleukin (IL)-10, interferon (IFN)-Ɣ] by peripheral blood mononuclear cells also was evaluated., Results: The veterinary extract showed a higher content of high molecular weight proteins, preferentially recognized by atopic dog sera. The fold-increases in Der f 15 and Der f 18 with respect to the human extract were 2.07 ± 0.32 and 1.63 ± 0.15, respectively. The veterinary extract showed higher biological potency (0.062 versus 0.132 µg required for 50% inhibition of dogs sera) compared to the human extract and induced significantly higher levels of IL-10 (1,780 pg/mL) and IFN-Ɣ (50.4 pg/mL) with respect to the negative control., Conclusions and Clinical Importance: A veterinary D. farinae extract with a higher content of dog major allergens was developed and in vitro efficacy demonstrated by immunological parameters., (© 2020 ESVD and ACVD.)

The aim of the study was to assess the expression of the immune checkpoint inhibitor programmed death-ligand 1 (PD-L1) in equine sarcoids (ES). Programmed death-ligand 1 is expressed by various cancer cells to block T cell-mediated elimination of tumor cells. Antibodies targeting human PD-L1 were tested by immunohistochemistry for their cross-reactivity with equine PD-L1 using formalin-fixed, paraffin-embedded tissues. Our results do not support an important role of PD-L1-mediated immune evasion in ES disease and hence do not offer a rationale for anti-PD-1/PD-L1-based immunotherapy against ES., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Sublingual immunotherapy (SLIT) has been deployed in humans and dogs; to the best of the authors' knowledge, there are no published studies about the use of SLIT in cats., Objectives: Evaluate the clinical efficacy of SLIT in atopic cats sensitized to dust and storage mites, assessing immunological changes associated with SLIT treatment., Animals: Twenty-two client-owned cats with clinical signs compatible with feline atopic dermatitis (fAD) and serum allergen-specific immunoglobulin (Ig)E against house dust and storage mites., Methods and Materials: Prospective, multicentre, open-label clinical trial. Individualized mite-specific SLIT was administered orally for 12 months. All cats underwent clinical examination to record SCORing feline allergic dermatitis (SCORFAD), pruritus Visual Analog Scale (pVAS) and serum allergen-specific IgE and IgG, every three months for 12 months., Results: Sixteen of 22 cats (73%) completed the study and three of six cats withdrawn from the study were included in an intention-to-treat analysis. SCORFAD and pVAS values decreased significantly from baseline (T0) to the third month of treatment (P = 0.0004 and P = 0.0013, respectively), with median total values ranging from 19 (6-44) (T0) to 2.5 (0-17) (T12) (P = 0.0001), and from 8 (6-10) (T0) to 2.3 (0-8) (T12) (P = 0.0001), respectively. Allergen-specific IgE values decreased significantly from the ninth month (T9) of treatment (P = 0.0032), with median scores decreasing from 56 (12-729) (T0) to 34 (0-158) (T12) (P = 0.0208). No significant differences in allergen-specific IgG values were observed throughout the study. No adverse effects related to the use of SLIT were reported., Conclusions and Clinical Importance: Sublingual immunotherapy should be considered a rapid, effective, safe and well-tolerated treatment in cats with feline atopic dermatitis fAD., (© 2021 ESVD and ACVD.)

Background: Feline allergic skin disease and asthma occur regularly in small animal practice., Objectives: To provide evidence-based recommendations for small animal practitioners on the treatment of feline atopic syndrome (FAS)., Methods and Materials: The authors reviewed the literature available before February 2020, prepared a detailed evidence-based literature review and made recommendations based on the evaluated evidence., Results: Sixty-six papers and abstracts were identified describing treatment interventions for FAS and evaluated to establish treatment recommendations. For many treatment options, the papers were retrospective, open studies or case reports., Conclusion and Clinical Relevance: In this review, there was good evidence for the efficacy of systemic glucocorticoids and ciclosporin, and limited evidence for the efficacy of topical glucocorticoids, oclacitinib and allergen-specific immunotherapy in feline atopic skin syndrome. Evidence pointed to low-to-moderate efficacy for antihistamines, fatty acids and palmitoyl ethanolamide. In feline asthma, there was good evidence for the efficacy of oral and inhaled glucocorticoids, and limited evidence of moderate efficacy for allergen-specific immunotherapy. Evidence supported low-to-moderate efficacy of mesenchymal stem cells, inhaled lidocaine and oclacitinib as treatments for feline asthma. For almost all therapeutic options (with the exception of glucocorticoids and ciclosporin), more randomised controlled trials are needed., (© 2021 The Authors. Veterinary Dermatology published by John Wiley & Sons Ltd on behalf of the European Society of Veterinary Dermatology and the American College of Veterinary Dermatology.)

Key advances in our understanding of immunobiology and the immunosuppressive mechanisms of the tumour microenvironment have led to significant breakthroughs in manipulating the immune system to successfully treat cancer. Remarkable therapeutic responses have occurred with tumours that carry a high mutational burden. In these cases, pre-existing tumour-specific T cells can be rejuvenated via checkpoint inhibition to eliminate tumours. Furthermore, durable remissions have been achieved in haematological malignancies following adoptive transfer of T cells that specifically target cell surface proteins where expression is restricted to the malignancy's cell of origin. Soft tissue sarcomas and bone sarcomas have a paucity of non-synonymous somatic mutations and do not commonly express known, targetable, tumour-specific antigens. Historically, soft tissue sarcomas have been considered immunologically 'cold' and as such, unlikely candidates for immune therapy. Here, we review the immune landscape of canine and feline sarcomas and the immunotherapeutic strategies that have been employed in veterinary clinical trials to improve patient outcome. We also provide insight into immunotherapeutic approaches being used to treat human sarcomas. Together, current data indicates that, rather than a barren immunological wasteland, sarcomas represent a field of opportunities for immunotherapies. Furthermore, we and others would suggest that strategic combinations of immunotherapeutic approaches may hold promise for more effective treatments for high grade soft tissue sarcomas and bone sarcomas., (© 2020 John Wiley & Sons Ltd.)

Inhibition of programmed death 1 (PD-1), expressed on activated T cells, can break through immune resistance and elicit durable responses in human melanoma as well as other types of cancers. Canine oral malignant melanoma is one of the most aggressive tumors bearing poor prognosis due to its high metastatic potency. However, there are few effective treatments for the advanced stages of melanoma in veterinary medicine. Only one previous study indicated the potential of the immune checkpoint inhibitor, anti-canine PD-L1 therapeutic antibody in dogs, and no anti-canine PD-1 therapeutic antibodies are currently available. Here, we developed two therapeutic antibodies, rat-dog chimeric and caninized anti-canine PD-1 monoclonal antibodies and evaluated in vitro functionality for these antibodies. Moreover, we conducted a pilot study to determine their safety profiles and clinical efficacy in spontaneously occurring canine cancers. In conclusion, the anti-canine PD-1 monoclonal antibody was relatively safe and effective in dogs with advanced oral malignant melanoma and other cancers. Thus, our study suggests that PD-1 blockade may be an attractive treatment option in canine cancers.

It is well-recognized that research capability in veterinary species is restricted by a lack of immunological reagents relative to the extensive toolboxes for small rodent biomedical model species and humans. This creates a barrier to the strategic development of disease control solutions for livestock, companion animals and wildlife that not only affects animal health but can affect human health by increasing the risk of transmission of zoonotic pathogens. There have been a number of projects aimed at reducing the capability gaps in the veterinary immunological toolbox, the majority of these focusing on livestock species. Various approaches have been taken to veterinary immunological reagent development across the globe and technological advances in molecular biology and protein biochemistry have accelerated toolbox development. While short-term funding initiatives can address specific gaps in capability, they do not account for long-term sustainability of reagents and databases that requires a different funding model. We review the past, present and future of the veterinary immunological toolbox with specific reference to recent developments discussed at the International Union of Immunological Societies (IUIS) Veterinary Immunology Committee (VIC) Immune Toolkit Workshop at the 12th International Veterinary Immunology Symposium (IVIS) in Seattle, USA, 16-19 August 2019. The future availability of these reagents is critical to research for improving animal health, responses to infectious pathogens and vaccine design as well as for important analyses of zoonotic pathogens and the animal /human interface for One Health initiatives., (Copyright © 2020 Entrican, Lunney, Wattegedera, Mwangi, Hope and Hammond.)

Meat of the South American camelids (SACs) llama and alpaca is an important source of animal protein and income for rural families in the Andes, and a product with significant growth potential for local and international markets. However, infestation with macroscopic cysts of the coccidian protozoon Sarcocystis aucheniae, a parasitosis known as SAC sarcocystosis, significantly hampers its commercialization. There are no validated methods to diagnose the presence of S. aucheniae cysts other than carcass examination. Moreover, there are no available drugs or vaccines to cure or prevent SAC sarcocystosis. Identification of relevant molecules that act at the host-pathogen interface can significantly contribute to the control of this disease. It has been shown for other pathogenic protozoa that glycosylphosphatidylinositol (GPI) is a critical molecule implicated in parasite survival and pathogenicity. This study focused on the identification of the enzymes that participate in the S. aucheniae GPI biosynthetic pathway and the repertoire of the parasite GPI-anchored proteins (GPI-APs). To this aim, RNA was extracted from parasite cysts and the transcriptome was sequenced and translated into amino acid sequences. The generated database was mined using sequences of well-characterized GPI biosynthetic enzymes of Saccharomyces cerevisiae and Toxoplasma gondii. Eleven enzymes predicted to participate in the S. aucheniae GPI biosynthetic pathway were identified. On the other hand, the database was searched for proteins carrying an N-terminal signal peptide and a single C-terminal transmembrane region containing a GPI anchor signal. Twenty-four GPI-anchored peptides were identified, of which nine are likely S. aucheniae-specific, and 15 are homologous to membrane proteins of other coccidians. Among the latter, 13 belong to the SRS domain superfamily, an extensive group of coccidian GPI-anchored proteins that mediate parasite interaction with their host. Phylogenetic analysis showed a great degree of intra- and inter-specific divergence among SRS family proteins. In vitro and in vivo experiments are needed to validate S. aucheniae GPI biosynthetic enzymes and GPI-APs as drug targets and/or as vaccine or diagnostic antigens., (© 2019 Blackwell Verlag GmbH.)

Sarcomas represent a group of genomically chaotic, highly heterogenous tumours of mesenchymal origin with variable mutational load. Conventional therapy with surgery and radiation therapy is effective for managing small, low-grade sarcomas and remains the standard therapeutic approach. For advanced, high-grade, recurrent, or metastatic sarcomas, systemic chemotherapy provides minimal benefit, therefore, there is a drive to develop novel approaches. The discovery of "Coley's toxins" in the 19th century, and their use to stimulate the immune system supported the application of unconventional therapies for the treatment of sarcomas. While promising, this initial work was abandoned and treatment paradigm and disease course of sarcomas was largely unchanged for several decades. Exciting new therapies are currently changing treatment algorithms for advanced carcinomas and melanomas, and similar approaches are being applied to advance the field of sarcoma research. Recent discoveries in subtype-specific cancer biology and the identification of distinct molecular targets have led to the development of promising targeted strategies with remarkable potential to change the landscape of sarcoma therapy in dogs. The purpose of this review article is to describe the current standard of care and limitations as well as emerging approaches for sarcoma therapy that span many of the most active paradigms in oncologic research, including immunotherapies, checkpoint inhibitors, and drugs capable of cellular metabolic reprogramming., (© 2019 John Wiley & Sons Ltd.)

Asthma is an important allergic lower-airway disease in cats affecting approximately 1% to 5% of the pet cat population. New diagnostics are being developed to help better differentiate asthma from other lower-airway diseases and improve monitoring. In addition, new treatments are being developed to help in refractory cases or in those cases in which traditional therapeutics are contraindicated. This article discusses potential pitfalls in the diagnosis of asthma. In addition, current literature investigating new diagnostic tests and therapies for feline asthma is reviewed., Competing Interests: Disclosure The author has nothing to disclose., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To determine the prevalence of positive allergen reactions in intradermal and IgE serological tests in dogs presenting to a dermatology referral centre in South Australia and the clinical efficacy of subsequent allergen-specific immunotherapy., Design: Retrospective study., Methods: Results from 108 intradermal allergy tests, 25 IgE serological assays and immunotherapy outcomes in 37 dogs were retrospectively analysed. Immunotherapy outcomes were determined as excellent, good, modest or failure using a global assessment of efficacy matrix which incorporated pruritus scores, lesion severity, medication requirements, and owner and clinician opinion., Results: The most common positive reactions in intradermal allergy tests were Red clover (59%), Dermatophagoides farinae (29%), Tyrophagus putrescentiae (28%), Yellow dock (25%) and Malassezia pachydermatis (24%). In the IgE serological tests, Yorkshire fog grass (40%), Yellow dock (36%), Kentucky bluegrass (36%) and T. putrescentiae (36%) were the most commonly reported positive results. The outcome of allergen-specific immunotherapy was judged to be excellent in 20% of dogs, good in 15%, modest in 18% and a failure in 47%., Conclusion: As has been reported in other geographical areas, environmental mites and plant pollens frequently gave positive reactions in allergy tests in South Australia. However, the prevalence of individual allergen reactions differed between intradermal and IgE serological tests, with M. pachydermatis being identified as a common cause of hypersensitivity in intradermal tests but not in IgE serological assays. Immunotherapy was judged to be a beneficial treatment in 35% of dogs but was essentially unsuccessful in 65%., (© 2019 Australian Veterinary Association.)

Background: Listeria monocytogenes is a promising therapeutic vaccine vector for cancer immunotherapy. Although highly attenuated, three cases of systemic listeriosis have been reported in people following treatment with Listeria-based therapeutic vaccines. This complication has thus far not been reported in canine patients., Case Presentation: A dog previously diagnosed with osteoblastic osteosarcoma was presented for care following administration of three doses of the Canine Osteosarcoma Vaccine-Live Listeria Vector. On routine staging chest radiographs, mild sternal lymphadenopathy and a right caudoventral thoracic mass effect were noted. Further evaluation of the mass effect with computed tomography and ultrasound revealed a cavitated mass associated with the 7th right rib. Aspirates of the mass cultured positive for Listeria monocytogenes. The mass and associated ribs were surgically removed. Histopathology was consistent with metastatic osteoblastic osteosarcoma. Treatment was continued with doxorubicin chemotherapy and at the time of publication, the dog was alive over 1 year following diagnosis with no evidence of further disease progression. Genotyping of the abscess-derived L. monocytogenes was consistent with the vaccine strain., Conclusions: This case represents the first veterinary case to describe development of a Listeria abscess following administration of a Listeria-based therapeutic vaccine.

Coccidiosis is a major gastrointestinal disease caused by several Eimeria species in floor raised chickens. Feeding an antibody to interleukin 10 (aIL-10) ameliorates the negative symptoms of coccidiosis in broilers, i.e., lack of weight gain, decreased feed conversion, and mortality. IL-10 signals by forming a ligand-receptor complex with IL-10 Receptor 1 (IL-10 R1) and IL-10 Receptor 2 (IL-10 R2). In this study, we hypothesize oral antibodies to the IL-10 receptors will neutralize the IL-10 signaling pathway equal to or better than aIL-10 to act as an oral anti-coccidiosis immunotherapy. A total of 5 sequential feed trials, set up as a 4 (diet antibody) × 2 (Eimeria challenge) factorial design, tested oral egg yolk antibodies to a total of 6 IL-10 R1 epitopes and 3 IL-10 R2 epitopes compared to a control antibody diet. A total of 10 pens of 5 chicks/pen/diet antibody/Eimeria challenge were housed for 21 d. On day 3 of age, chicks were either infected or not infected with a 10× dose of an Eimeria vaccine containing Eimeria acervulina, Eimeria tenella, and Eimeria maxima. Pen feed consumption and mean body weights were assessed weekly (d1, d7, d14, and d21); fecal oocyst shedding was assessed on day 10. Data were analyzed using a 2-way ANOVA. No significant interaction on chick weight was observed in chicks fed IL-10 R1 antibodies compared to chicks fed the control antibody was observed. In studies evaluating aIL-10 R2 oral antibodies, infected chicks fed aIL-10 R2: epitope 1 overcame the negative effects of Eimeria infection and had similar 21-d body weight to uninfected chicks (P4 = 0.07). We hypothesized that feeding oral antibodies to the IL-10 receptors would result in equivalent anti-coccidial benefits to aIL-10. However, none of the 6 antibodies to IL-10 R1 epitopes yielded any benefits during Eimeria infection compared to controls. A total of 2 oral antibodies to IL-10 R2 showed promising results equivalent to the aIL-10 immunotherapeutic. Immunofluorescence staining shows that the IL-10R2 significantly increases in abundance in response to Eimeria infection, whereas IL-10R1 does not., (© 2019 Poultry Science Association Inc.)

Lymphoma is a common disease in companion animals. Although conventional chemotherapy has the potential to induce remission and prolong life, relapse is common, and novel treatments are needed to improve outcome. This review discusses recent modifications/adjustments to conventional standard of care therapy for canine and feline lymphoma, as well as cutting-edge immunotherapy and small-molecule-based approaches that are in varying stages of regulatory approval., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The enhanced understanding of immunology experienced over the last 4 decades afforded through the tools of molecular biology has recently translated into cancer immunotherapy becoming one of the most exciting and rapidly expanding fields. Human cancer immunotherapy is now recognized as one of the pillars of treatment alongside surgery, radiation, and chemotherapy. The field of veterinary cancer immunotherapy has also rapidly advanced in the last decade with a handful of commercially available products and a plethora of investigational cancer immunotherapies that will hopefully expand the veterinary oncology treatment toolkit over time., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Leishmaniosis due to Leishmania infantum is a complex infection that can affect both humans and dogs, and present a wide range of clinical signs and clinicopathological abnormalities. The conventional treatment of this disease is challenging due to the fact that complete parasitological cure commonly does not occur. Furthermore, treatment of the disease with the conventionally used drugs has several shortcomings. These include the need for long-term treatment, side effects and the formation of drug resistance. Moreover, it is important to highlight that the host immune responses play a crucial role in the outcome of this infection. For this reason, the use of immunotherapy in clinical leishmaniosis to improve the result of treatment with the conventional anti-leishmanial drugs by enhancing the immune response is imperative. The aim of this review is to provide a comparative overview of the wide range of immunotherapeutical approaches and strategies for the treatment of L. infantum infection in animals focusing on dogs., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background/aim: Previous work in rodent models showed that an autologous tissue vaccine is both a safe and effective approach for treating cancer; however, as a translational step, safety must first be evaluated in a more clinically-relevant model., Materials and Methods: An autologous immunotherapy produced from resected tumors, was evaluated in a clinically-relevant canine model to assess safety. Ninety-three dogs with spontaneously occurring tumors received vaccination with inactivated autologous tumor tissue combined with an adjuvant of particulate porcine small intestinal submucosa extracellular matrix (SIS-ECM). Patients were followed to assess the occurrence of adverse events, overall survival, and tumor recurrence and/or metastasis., Results: A small number (12%) of patients experienced limited, mild pyrexia, injection site swelling, or lethargy, all resolving without clinical intervention., Conclusion: Autologous whole cell cancer immunotherapy can be used safely in the canine model of cancer and represents a safe approach for the treatment for cancer., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Context: Exosomes secreted by tumor cells are a good source of cellular components that stimulate the immune response, such as alarmins (mRNA, tetraspanins (CD9, CD63, CD81), heat-shock proteins, major histocompatibility complex class I molecules) and tumor-associated antigens. These properties permit to pulsed dendritic cells in the immunotherapy for many cancers types. The aim of this study was to demonstrate the use of exosomes derived from canine transmissible venereal tumor (CTVT) as an antigen to pulsed dendritic cells and its administration in dogs with CTVT as treatment against this disease. Material and methods: From primary culture of CTVT cells the exosomes were isolated and characterized by scanning electron microscopy assay, dot blot and protein quantification. The monocytes of each patient were differentiated to dendritic cells (DC) and pulsed with CTVT exosomes (CTVTE). Phagocytosis, tumor size, populations of lymphocytes and IFN-c levels were evaluated. Results: The CTVTE showed a size around 90 nm. CD81, CD63, CD9 and Hsp70 were expressed. Monocytes showed an expression of 85.71% for CD14 + , 12.3% for CD80 + , 0.1% for CD83 + and 0.8% for DLA-II. In DC 5.1% for CD14 + , 86.7% for CD80 + , 90.1% for CD83 + and 92.6% for DLA-II and a phagocytosis of 63% was obtained by FITC Dextran test. No side effects were observed in the experimental groups with our therapy. Tumor regression was of 100% at the seventh week, as well as an increase in the level of IFN- γ (142 pg/ml), and CD4 + (28%) and CD8 + (34%) cell percentage. Discusion and conclusion: These results have shown that DC pulsed with tumor exosomes induce regression of the TVT in dogs.

Background: Canine atopic dermatitis (cAD) is associated with an imbalance between multiple T lymphocytes and cytokines. Ex vivo boosted immune cell (EBIC) therapy is the sequential administration of ex vivo cultured and activated lymphocytes to patients to improve immune function., Objective: This pilot study aimed to assess the safety of EBIC therapy and demonstrate its efficacy as a novel treatment for cAD., Animals: Ten dogs with AD., Methods and Materials: The phenotypes of the immune cells before and after ex vivo culture were analysed by flow cytometry. EBICs (1.0-5.0 × 10 8 cells/animal) were administered to dogs every two weeks, with a total of six injections. The cAD extent and severity index (CADESI)-03 and pruritus scores were calculated to evaluate the efficacy of EBIC therapy for cAD. For safety assessment, regular blood examination was conducted, and any adverse events recorded. The serum levels of interleukin (IL)-4, IL-10, IL-31 and interferon-gamma (IFN-γ) were evaluated., Results: The cells expanded by an average of 57.52-fold and the proportions of CD8 + cells and IFN-γ-producing cells significantly increased after ex vivo culture. Sequential EBIC therapy improved CADESI-03, and pruritus scores significantly. After stopping treatment the improvement rates increased for the CADESI score and were maintained for the pruritus score. There were no significant changes in cytokine levels. No significant adverse events were observed., Conclusions and Clinical Significance: EBIC therapy is a safe and efficient treatment for cAD. This therapy could correct the immunological imbalance in dogs with AD by infusing activated T lymphocytes., (© 2018 The Authors. Veterinary Dermatology published by John Wiley & Sons Ltd on behalf of the ESVD and ACVD.)

Whole tumor cell lysates consist of a mixture of tumor antigens and danger associated molecular patterns (DAMPs) that can be used for dendritic cell maturation and consequently for the activation of a polyclonal T cell-specific tumor response. We evaluated the in vitro efficacy of three different preparations of canine transmissible venereal tumor (TVT) cell lysates: hypochlorous acid-whole tumor cell lysates (HOCl-L), heat shock-whole tumor cell lysates (HS-L), and freeze-thaw cycles-whole tumor cell lysates (FT-L) for the maturation of canine-derived dendritic cells. Our results showed calreticulin, HSP70, and HSP90 release in the three tumor lysates preparations (HOCl-L, HS-L, and FT-L); however, HMGB1 was detected only in HOCl-L and FT-L. Additionally, the uptake by HOCl-L pulsed dendritic cell (DC) increased compared to HS-L and FT-L pulsed DC; and dendritic cell maturation was confirmed by the appropriate cell surface markers (CD11c, CD80, CD83, and MHCII). Furthermore, dendritic cells pulsed with HOCl-L, HS-L or FT-L were cultured with canine lymphocytes. There was an increase of Th1-type cytokines (IL-12, TNF-α, and IFN-γ), in all the tumor cell lysates co-cultures, this correlates with T lymphocyte activation and cytotoxic response. Our data confirm that TVT cell lysates can induce functional canine-DC and that HOCl-L is the most effective one. This preparation of TVT cell lysates with HOCl is an attractive approach that allows the recognition of neoantigens as potential tumor targets and DC priming and therefore could be used for cancer immunotherapy against TVT., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

OBJECTIVE To evaluate the effect of an immunotherapeutic product on concentrations of anti-Pythium insidiosum antibodies in dogs. ANIMALS 7 healthy hound-crossbreds. PROCEDURES Antibody concentrations were evaluated before (day 0) and after administration of the immunotherapeutic product. The immunotherapeutic product was administered on days 0, 7, and 21. Serum was obtained on days 0, 7, 14, 21, 28, 35, 42, 49, and 56. Anti-P insidiosum antibody concentrations were measured and reported as the percentage positivity relative to results for a strongly positive control serum. RESULTS Mean ± SD percentage positivity before administration of the immunotherapeutic product was 7.45 ± 3.02%. There was no significant change in anti-P insidiosum antibody concentrations after administration of the product, with percentage positivity values in all dogs remaining within the range expected for healthy dogs (3% to 15%). CONCLUSIONS AND CLINICAL RELEVANCE Administration of the immunotherapeutic product to healthy dogs in accordance with the manufacturer's suggested protocol did not induce a significant change in anti-P insidiosum antibody concentrations. These results suggested that administration of the immunotherapeutic product may not interfere with postadministration serologic monitoring. However, further investigations will be required to determine whether there is a similar effect in naturally infected dogs.

Better tools are necessary to eliminate visceral leishmaniasis (VL). Modeling studies for regional Leishmania elimination indicate that an effective vaccine is a critical tool. Dogs are the reservoir host of L. infantum in Brazil and the Mediterranean basin, and therefore are an important target for public health interventions as well as a relevant disease model for human VL. No vaccine has been efficacious as an immunotherapy to prevent progression of already diagnostically positive individuals to symptomatic leishmaniasis. We performed a double-blinded, block-randomized, placebo-controlled, vaccine immunotherapy trial testing the efficacy of a recombinant Leishmania A2 protein, saponin-adjuvanted, vaccine, LeishTec®, in owned hunting dogs infected with L. infantum. The primary outcome was reduction of clinical progression, with reduction of mortality as a secondary outcome. Vaccination as an immunotherapy reduced the risk of progression to clinically overt leishmaniasis by 25% in asymptomatic dogs (RR: 1.33 95% C.I. 1.009-1.786 p-value: 0.0450). Receiving vaccine vs. placebo reduced all-cause mortality in younger asymptomatic dogs by 70% (RR: 3.19 95% C.I.: 1.185-8.502 p-value = 0.0245). Vaccination of infected-healthy animals with an anti-Leishmania vaccine significantly reduced clinical progression and decreased all-cause mortality. Use of vaccination in infected-healthy dogs can be a tool for Leishmania control., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Polymerized allergoids coupled to nonoxidized mannan (PM-allergoids) are novel allergen preparations used for immunotherapy., Objective: To evaluate PM-allergoids as an alternative immunotherapy for dogs with canine atopic dermatitis (cAD) associated with serological responses to Dermatophagoides farinae allergens., Animals: Sixteen dogs with history and clinical signs of cAD; positive on serum allergen specific IgE testing to D. farinae. Twelve dogs were, in addition, positive to Acarus siro and/or Lepidoglyphus destructor., Methods and Materials: A prospective pilot study with no control group. PM-allergoids were administered by subcutaneous injection over a 10 month period. A pruritus Visual Analog Scale (pVAS) and medication scores were evaluated. Adverse reactions were recorded., Results: The median value of the pVAS of the dogs decreased from 0.6 to 0.2 with a median of 67% improvement over the first three months (P < 0.0001). The individual improvement for each dog was greater than 60%. No major adverse effects were observed., Conclusions and Clinical Importance: Allergen-specific immunotherapy using an allergoid coupled to nonoxidized mannan may be an effective alternative for the management of cAD., (© 2018 ESVD and ACVD.)

Canine nodal marginal zone lymphoma (nMZL) is classified as an indolent lymphoma. Such lymphomas are typified by low mitotic rate and slow clinical progression. While the clinical behaviour of canine splenic MZL has been described, characterized by an indolent course and a good prognosis following splenectomy, there are no studies specifically describing nMZL. The aim of this study was to describe the clinical features of and outcome for canine nMZL. Dogs with histologically confirmed nMZL undergoing a complete staging work-up (including blood analysis, flow cytometry [FC] on lymph node [LN], peripheral blood and bone marrow, imaging, histology and immunohistochemistry on a surgically removed peripheral LN) were retrospectively enrolled. Treatment consisted of chemotherapy or chemo-immunotherapy. Endpoints were response rate (RR), time to progression (TTP) and lymphoma-specific survival (LSS). A total of 35 cases were enrolled. At diagnosis, all dogs showed generalized lymphadenopathy. One-third was systemically unwell. All dogs had stage V disease; one-third also had extranodal involvement. The LN population was mainly composed of medium-sized CD21+ cells with scant resident normal lymphocytes. Histology revealed diffuse LN involvement, referring to "late-stage" MZL. Median TTP and LSS were 149 and 259 days, respectively. Increased LDH activity and substage b were significantly associated with a shorter LSS. Dogs with nMZL may show generalized lymphadenopathy and an advanced disease stage. Overall, the outcome is poor, despite the "indolent" designation. The best treatment option still needs to be defined., (© 2017 John Wiley & Sons Ltd.)

Clostridium novyi-NT (CVN-NT) spores germinate in hypoxic regions of tumors and have successfully cured induced neoplasia in mouse models and resulted in objective tumor responses in naturally developing neoplasia in the dog. The objective of this pilot, descriptive, prospective, clinical investigation, was to evaluate and describe the immune response to CNV-NT spores to better understand which immune pathways might play a role in the response to this bacteriolytic immunotherapy. Intratumoral injection of CNV-NT spores result in increased phagocytosis and NK cell-like function after treatment. Intravenous injection of CNV-NT spores resulted in increased LPS-induced TNF-α production, LTA-induced IL-10 production and NK cell-like function post-treatment. Increased NK cell-like function was sustained to 28 (intratumoral) or 56 (intravenous) days post-treatment, and increased phagocytic function was sustained to 28 days post-treatment suggesting that CNV-NT spores induce longer-term immune cell function changes. Future investigations evaluating long-term immune system changes and associations between immune function and tumor remission rates should include evaluation of these pathways.

Background: Clostridium novyi-NT (CNV-NT), has shown promise as a bacterolytic therapy for solid tumors in mouse models and in dogs with naturally developing neoplasia. Factors that impact the immunologic response to therapy are largely unknown. The goal of this pilot study was to determine if plasma immune biomarkers, immune cell function, peripheral blood cytological composition and tumor characteristics including evaluation of a PET imaging surrogate of tumor tissue hypoxia could predict which dogs with naturally developing naïve neoplasia would develop an inflammatory response to CNV-NT., Results: Dogs that developed an inflammatory response to CNV-NT had a higher heart rate, larger gross tumor volume, greater tumor [ 64 Cu]ATSM SUV Max , increased constitutive leukocyte IL-10 production, more robust NK cell-like function and greater peripheral blood lymphocyte counts compared to dogs that did not develop an inflammatory response to CNV-NT. Of these, unstimulated leukocyte IL-10 production, heart rate, and gross tumor volume appeared to be the best predictors of which dogs will develop an inflammatory response to CNV-NT., Conclusions: Development of inflammation in response to CNV-NT is best predicted by pretreatment unstimulated leukocyte IL-10 production, heart rate, and gross tumor volume.