Search

Background: Pet dogs spontaneously develop lymphoma. An anthracycline-based multidrug chemotherapy regimen represents the treatment cornerstone; however, cure is rarely achieved. We have been treating dogs with B-cell lymphoma with an autologous vaccine (APAVAC®) and CHOP-based chemotherapy since 2011., Methods: To better characterize the safety and efficacy of APAVAC®, and to find the best candidates for immunotherapy, we designed a retrospective study on all dogs treated with chemo-immunotherapy to date and compared them with those dogs treated with chemotherapy only. All dogs were completely staged and re-staged at the end of treatment. The primary endpoint was the effectiveness of chemo-immunotherapy, measured as time to progression (TTP), lymphoma-specific survival (LSS), and 1-, 2-, and 3-year survival rates. The secondary objective was safety., Results: Three hundred dogs were included: 148 (49.3%) received chemotherapy and 152 (50.7%) chemo-immunotherapy. Overall, the latter survived significantly longer (median LSS, 401 vs 220; P <  0.001). Among dogs with diffuse large B-cell lymphoma, the 1-, 2- and 3-year survival rates were 20, 13 and 8% for chemotherapy, and 51, 19 and 10% for chemo-immunotherapy. The benefit of chemo-immunotherapy was particularly relevant in dogs with concurrent high serum LDH, stage V, substage a disease and not previously treated with steroids (median LSS, 480 vs 85 days; P <  0.001). Among dogs with nodal marginal zone lymphoma, those having at least 3 of the aforementioned characteristics significantly benefited from chemo-immunotherapy (median LSS, 680 vs 160 days, P <  0.001). The 1-, 2- and 3-year survival rates were 30, 16 and 10% for chemotherapy, and 55, 28 and 10% for chemo-immunotherapy. Among dogs with follicular lymphoma, lack of immunotherapy administration was the only variable significantly associated with increased risk of tumor-related death. Chemo-immunotherapy was remarkably well tolerated, with no local or systemic adverse events., Conclusions: Overall, the addition of immunotherapy to a traditional CHOP protocol is associated with improved outcome in dogs with B-cell lymphoma, regardless of histotype and evaluated prognostic factors. Moreover, the identikit of the best candidate for immune-therapy was delineated for the most common histotypes. The study also confirms the excellent tolerability of the vaccine.

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.)

Purpose: To determine the safety of an approach to immunologically enhance local treatment of hepatocellular cancer (HCC) by combining nonlethal radiation, local regional therapy with intratumoral injection, and systemic administration of a potent Toll-like receptor (TLR) immune adjuvant., Methods: Patients with HCC not eligible for liver transplant or surgery were subject to: 1) 3 fractions of 2-Gy focal nonlethal radiation to increase tumor antigen expression, 2) intra-/peri-tumoral (IT) injection of the TLR3 agonist, polyinosinic-polycytidylic acid polylysine carboxymethylcellulose (poly-ICLC), to induce an immunologic "danger" response in the tumor microenvironment with local regional therapy, and 3) systemic boosting of immunity with intramuscular poly-ICLC. Primary end points were safety and tolerability; secondary end points were progression-free survival (PFS) and overall survival (OS) at 6 months, 1 year, and 2 years., Results: Eighteen patients with HCC not eligible for surgery or liver transplant were treated. Aside from 1 embolization-related severe adverse event, all events were ≤grade II. PFS was 66% at 6 months, 39% at 12 months, and 28% at 24 months. Overall 1-year survival was 69%, and 2-year survival 38%. In patients <60 years old, 2-year survival was 62.5% vs. 11.1% in patients aged >60 years ( P <0.05). Several patients had prolonged PFS and OS., Conclusion: Intra-tumoral injection of the TLR3 agonist poly-ICLC in patients with HCC is safe and tolerable when combined with local nonlethal radiation and local regional treatment. Further work is in progress to evaluate if this approach improves survival compared to local regional treatment alone and characterize changes in anticancer immunity., Competing Interests: Disclosure AMS is an employee of Oncovir and owns stock in the company. The other authors have no conflicts of interests in this work and not made any financial investment, nor have received direct funds from Oncovir Pharmaceutical.

Approximately nine out of ten breast cancer-related deaths are attributable to metastasis. Yet, less than 4% of breast cancer patients are initially diagnosed with metastatic cancer. Therefore, the majority of breast cancer-related deaths are due to recurrence and progression of non-metastatic disease. There is tremendous clinical opportunity for novel adjuvant strategies, such as immunotherapies, that have the potential to prevent progressive recurrences. In particular, autologous tumor cell-based vaccines (ATCVs) can train a patient's immune system to recognize and eliminate occult disease. ATCVs have several advantages including safety, multivalency and patient specificity. Furthermore, because lumpectomy or mastectomy is indicated for the vast majority of breast cancer patients, resected tumors offer a readily available, patient-specific source of tumor antigen. Disadvantages of ATCVs include poor immunogenicity and production inconsistencies. This review summarizes recent progress in the development of autologous breast tumor vaccines and offers insight for overcoming existing limitations.

Tumor as source of tumor associated antigens (TAA) and sentinel lymph node (SLN) configure the first interaction between the malignant disease and the patient's immune system. As consequence of this interaction, a local immune response is elicited inside the SLN. Tumor's cytokines reach the SLN conditioning its cellular microenvironment to produce local permissive immune responses. This local tolerogenic immunity is decisional because it starts a systemic also permissive immunity. The tumor progresses.To counteract this mechanism, we have designed a medical procedure to create an immunotherapeutic site (ITS) that reproduces, distantly from the tumor, a TAA source and a draining lymph node but with a cellular microenvironment conditioned to promote local protective instead of permissive immune responses. Due to ITS decisional role, this local protective immunity starts a systemic anti-tumoral immune response.In progressive ovarian cancer, we tested an ITS using the autologous thermostable hemoderivative-cancer vaccine as TAA source and granulocyte macrophage-colony stimulant factor plus etoposide, injected both at the vaccination site, as conditioner of the draining lymph node cellularity. The immunophenotyping of lymph node cell populations showed that ITS acquired a locally protective immune profile T-regulatory-cells/activated-antigen presenting-cells and systemically increased the antiprogressive effect of the tested vaccine.