66 results on '"D'Alise, Anna Morena"'
Search Results
52. Mucosal delivery of a vectored RSV vaccine is safe and elicits protective immunity in rodents and nonhuman primates
- Author
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Pierantoni, Angiolo, primary, Esposito, Maria Luisa, additional, Ammendola, Virginia, additional, Napolitano, Federico, additional, Grazioli, Fabiana, additional, Abbate, Adele, additional, del Sorbo, Mariarosaria, additional, Siani, Loredana, additional, D'Alise, Anna Morena, additional, Taglioni, Alessandra, additional, Perretta, Gemma, additional, Siccardi, Antonio, additional, Soprana, Elisa, additional, Panigada, Maddalena, additional, Thom, Michelle, additional, Scarselli, Elisa, additional, Folgori, Antonella, additional, Colloca, Stefano, additional, Taylor, Geraldine, additional, Cortese, Riccardo, additional, Nicosia, Alfredo, additional, Capone, Stefania, additional, and Vitelli, Alessandra, additional
- Published
- 2015
- Full Text
- View/download PDF
53. Fusion of HCV Nonstructural Antigen to MHC Class II–associated Invariant Chain Enhances T-cell Responses Induced by Vectored Vaccines in Nonhuman Primates
- Author
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Capone, Stefania, primary, Naddeo, Mariarosaria, additional, D'Alise, Anna Morena, additional, Abbate, Adele, additional, Grazioli, Fabiana, additional, Del Gaudio, Annunziata, additional, Del Sorbo, Mariarosaria, additional, Esposito, Maria Luisa, additional, Ammendola, Virginia, additional, Perretta, Gemma, additional, Taglioni, Alessandra, additional, Colloca, Stefano, additional, Nicosia, Alfredo, additional, Cortese, Riccardo, additional, and Folgori, Antonella, additional
- Published
- 2014
- Full Text
- View/download PDF
54. In vivo generation of transplantable human hematopoietic cells from induced pluripotent stem cells
- Author
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Amabile, Giovanni, primary, Welner, Robert S., additional, Nombela-Arrieta, Cesar, additional, D'Alise, Anna Morena, additional, Di Ruscio, Annalisa, additional, Ebralidze, Alexander K., additional, Kraytsberg, Yevgenya, additional, Ye, Min, additional, Kocher, Olivier, additional, Neuberg, Donna S., additional, Khrapko, Konstantin, additional, Silberstein, Leslie E., additional, and Tenen, Daniel G., additional
- Published
- 2013
- Full Text
- View/download PDF
55. Reversine, a novel Aurora kinases inhibitor, inhibits colony formation of human acute myeloid leukemia cells
- Author
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D'Alise, Anna Morena, primary, Amabile, Giovanni, additional, Iovino, Mariangela, additional, Di Giorgio, Francesco Paolo, additional, Bartiromo, Marta, additional, Sessa, Fabio, additional, Villa, Fabrizio, additional, Musacchio, Andrea, additional, and Cortese, Riccardo, additional
- Published
- 2008
- Full Text
- View/download PDF
56. Adenoviral-based vaccine promotes neoantigen-specific CD8+T cell stemness and tumor rejection
- Author
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D’Alise, Anna Morena, Brasu, Nadia, De Intinis, Carlo, Leoni, Guido, Russo, Valentina, Langone, Francesca, Baev, Denis, Micarelli, Elisa, Petiti, Luca, Picelli, Simone, Fakih, Marwan, Le, Dung T., Overman, Michael J., Shields, Anthony F., Pedersen, Katrina S., Shah, Manish A., Mukherjee, Sarbajit, Faivre, Thea, Delaite, Patricia, Scarselli, Elisa, and Pace, Luigia
- Abstract
Upon chronic antigen exposure, CD8+T cells become exhausted, acquiring a dysfunctional state correlated with the inability to control infection or tumor progression. In contrast, stem-like CD8+T progenitors maintain the ability to promote and sustain effective immunity. Adenovirus (Ad)–vectored vaccines encoding tumor neoantigens have been shown to eradicate large tumors when combined with anti–programmed cell death protein 1 (αPD-1) in murine models; however, the mechanisms and translational potential have not yet been elucidated. Here, we show that gorilla Ad vaccine targeting tumor neoepitopes enhances responses to αPD-1 therapy by improving immunogenicity and antitumor efficacy. Single-cell RNA sequencing demonstrated that the combination of Ad vaccine and αPD-1 increased the number of murine polyfunctional neoantigen-specific CD8+T cells over αPD-1 monotherapy, with an accumulation of Tcf1+stem-like progenitors in draining lymph nodes and effector CD8+T cells in tumors. Combined T cell receptor (TCR) sequencing analysis highlighted a broader spectrum of neoantigen-specific CD8+T cells upon vaccination compared to αPD-1 monotherapy. The translational relevance of these data is supported by results obtained in the first 12 patients with metastatic deficient mismatch repair (dMMR) tumors vaccinated with an Ad vaccine encoding shared neoantigens. Expansion and diversification of TCRs were observed in post-treatment biopsies of patients with clinical response, as well as an increase in tumor-infiltrating T cells with an effector memory signature. These findings indicate a promising mechanism to overcome resistance to PD-1 blockade by promoting immunogenicity and broadening the spectrum and magnitude of neoantigen-specific T cells infiltrating tumors.
- Published
- 2022
- Full Text
- View/download PDF
57. A cluster of coregulated genes determines TGF-βinduced regulatory T-cell (Treg) dysfunction in NOD mice.
- Author
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D'Alise, Anna Morena, Ergun, Ayla, Hill1, Jonathan A., Mathis, Diane, and Benoist, Christophe
- Subjects
- *
GENES , *T cells , *LYMPH nodes , *LYMPHOID tissue , *CELL differentiation - Abstract
Foxp3+ regulatory T cells (Tregs) originate in the thymus, but the Treg phenotype can also be induced in peripheral lymphoid organs or in vitro by stimulation of conventional CD4+ T cells with IL-2 and TGF-β. There have been divergent reports on the suppressive capacity of these TGF-Treg cells. We find that TGF-Tregs derived from diabetes-prone NOD mice, although expressing normal Foxp3 levels, are uniquely defective in suppressive activity, whereas TGF-Tregs from control strains (B6g7) or ex vivo Tregs from NOD mice all function normally. Most Treg-typical transcripts were shared by NOD or B6g7 TGF-Tregs, except for a small group of differentially expressed genes, including genes relevant for suppressive activity (Lrrc32, Ctla4, and Cd73). Many of these transcripts form a coregulated cluster in a broader analysis of T-cell differentiation. The defect does not map to idd3 or idd5 regions. Whereas Treg cells from NOD mice are normal in spleen and lymph nodes, the NOD defect is observed in locations that have been tied to pathogenesis of diabetes (small intestine lamina propria and pancreatic lymph node). Thus, a genetic defect uniquely affects a specific Treg subpopulation in NOD mice, in a manner consistent with a role in determining diabetes susceptibility. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
58. Adenoviral vaccine targeting multiple neoantigens as strategy to eradicate large tumors combined with checkpoint blockade.
- Author
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D'Alise, Anna Morena, Leoni, Guido, Cotugno, Gabriella, Troise, Fulvia, Langone, Francesca, Fichera, Imma, De Lucia, Maria, Avalle, Lidia, Vitale, Rosa, Leuzzi, Adriano, Bignone, Veronica, Di Matteo, Elena, Tucci, Fabio Giovanni, Poli, Valeria, Lahm, Armin, Catanese, Maria Teresa, Folgori, Antonella, Colloca, Stefano, Nicosia, Alfredo, and Scarselli, Elisa
- Abstract
Neoantigens (nAgs) are promising tumor antigens for cancer vaccination with the potential of inducing robust and selective T cell responses. Genetic vaccines based on Adenoviruses derived from non-human Great Apes (GAd) elicit strong and effective T cell-mediated immunity in humans. Here, we investigate for the first time the potency and efficacy of a novel GAd encoding multiple neoantigens. Prophylactic or early therapeutic vaccination with GAd efficiently control tumor growth in mice. In contrast, combination of the vaccine with checkpoint inhibitors is required to eradicate large tumors. Gene expression profile of tumors in regression shows abundance of activated tumor infiltrating T cells with a more diversified TCR repertoire in animals treated with GAd and anti-PD1 compared to anti-PD1. Data suggest that effectiveness of vaccination in the presence of high tumor burden correlates with the breadth of nAgs-specific T cells and requires concomitant reversal of tumor suppression by checkpoint blockade. Vaccination against neo-antigens has resulted in an effective antitumor response in several models. Here, the authors show that delivery of larger sets of neo-antigens using an adenovirus-based vaccination platform, results in much better tumor protection when combined with checkpoint blockade in a mouse model of advanced disease. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
59. Mucosal delivery of a vectored RSV vaccine is safe and elicits protective immunity in rodents and nonhuman primates
- Author
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Angiolo Pierantoni1, Maria Luisa Esposito1, Virginia Ammendola1, Federico Napolitano1, Fabiana Grazioli1, Adele Abbate1, Mariarosaria del Sorbo1, Loredana Siani1, Anna Morena D'Alise1, Alessandra Taglioni3, Gemma Perretta3, Antonio Siccardi4, Elisa Soprana4, Maddalena Panigada4, Michelle Thom2, Elisa Scarselli1, Antonella Folgori1, Stefano Colloca1, Geraldine Taylor2, Riccardo Cortese1, 7, Alfredo Nicosia1, 5, 6, Stefania Capone1, Alessandra Vitelli1, Pierantoni, Angiolo, Esposito, Maria Luisa, Ammendola, Virginia, Napolitano, Federico, Grazioli, Fabiana, Abbate, Adele, del Sorbo, Mariarosaria, Siani, Loredana, D'Alise, Anna Morena, Taglioni, Alessandra, Perretta, Gemma, Siccardi, Antonio, Soprana, Elisa, Panigada, Maddalena, Thom, Michelle, Scarselli, Elisa, Folgori, Antonella, Colloca, Stefano, Taylor, Geraldine, Cortese, Riccardo, Nicosia, Alfredo, Capone, Stefania, and Vitelli, Alessandra
- Subjects
Cellular immunity ,Modified vaccinia Ankara ,lcsh:QH426-470 ,viruses ,Virus ,Article ,Lower respiratory tract infection ,medicine ,Genetics ,lcsh:QH573-671 ,Neutralizing antibody ,Molecular Biology ,biology ,business.industry ,lcsh:Cytology ,Immunogenicity ,virus diseases ,respiratory system ,medicine.disease ,Virology ,3. Good health ,Vaccination ,lcsh:Genetics ,medicine.anatomical_structure ,Immunology ,biology.protein ,Molecular Medicine ,business ,Respiratory tract - Abstract
Respiratory Syncytial Virus (RSV) is a leading cause of severe respiratory disease in infants and the elderly. No vaccine is presently available to address this major unmet medical need. We generated a new genetic vaccine based on chimpanzee Adenovirus (PanAd3-RSV) and Modified Vaccinia Ankara RSV (MVA-RSV) encoding the F, N, and M2-1 proteins of RSV, for the induction of neutralizing antibodies and broad cellular immunity. Because RSV infection is restricted to the respiratory tract, we compared intranasal (IN) and intramuscular (M) administration for safety, immunogenicity, and efficacy in different species. A single IN or IM vaccination completely protected BALB/c mice and cotton rats against RSV replication in the lungs. However, only IN administration could prevent infection in the upper respiratory tract. IM vaccination with MVA-RSV also protected cotton rats from lower respiratory tract infection in the absence of detectable neutralizing antibodies. Heterologous prime boost with PanAd3-RSV and MVA-RSV elicited high neutralizing antibody titers and broad T-cell responses in nonhuman primates. In addition, animals primed in the nose developed mucosal IgA against the F protein. In conclusion, we have shown that our vectored RSV vaccine induces potent cellular and humoral responses in a primate model, providing strong support for clinical testing.
- Published
- 2015
60. Fusion of HCV non-structural antigen to MHC Class II associated invariant chain enhances T cell responses induced by vectored vaccines in non-human primates
- Author
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Stefania Capone 1, Mariarosaria Naddeo 1, Anna Morena D'Alise 1, Adele Abbate 1, Fabiana Grazioli 1, Annunziata Del Gaudio 1, Mariarosaria del Sorbo 1, Maria Luisa Esposito 1, Virginia Ammendola 1, Gemma Perretta 2, Alessandra Taglioni 2, Stefano Colloca 1, Alfredo Nicosia 1, 3, 4, Riccardo Cortese 1, 5, Antonella Folgori 1, Capone, Stefania, Naddeo, Mariarosaria, D'Alise, Anna Morena, Abbate, Adele, Grazioli, Fabiana, Del Gaudio, Annunziata, Del Sorbo, Mariarosaria, Esposito, Maria Luisa, Ammendola, Virginia, Perretta, Gemma, Taglioni, Alessandra, Colloca, Stefano, Nicosia, Alfredo, Cortese, Riccardo, and Folgori, Antonella
- Subjects
Modified vaccinia Ankara ,Hepacivirus ,CD8-Positive T-Lymphocytes ,Mice ,0302 clinical medicine ,Drug Discovery ,Antigens, Viral ,Vaccines ,0303 health sciences ,Medicine (all) ,Immunogenicity ,Pan troglodyte ,Hepatitis C ,3. Good health ,Adenovirus vaccine ,medicine.anatomical_structure ,Molecular Medicine ,Original Article ,Human ,medicine.drug ,Pan troglodytes ,Recombinant Fusion Proteins ,T cell ,Genes, MHC Class II ,Biology ,Major histocompatibility complex ,Adenoviridae ,Viral vector ,Interferon-gamma ,03 medical and health sciences ,Genetic ,Antigen ,Genetics ,medicine ,Animals ,Humans ,Molecular Biology ,030304 developmental biology ,Pharmacology ,Hepaciviru ,Animal ,Drug Discovery3003 Pharmaceutical Science ,Histocompatibility Antigens Class II ,CD8-Positive T-Lymphocyte ,Virology ,Antigens, Differentiation, B-Lymphocyte ,Immunology ,biology.protein ,Vaccine ,CD8 ,Recombinant Fusion Protein ,030215 immunology - Abstract
Despite viral vectors being potent inducers of antigen-specific T cells, strategies to further improve their immunogenicity are actively pursued. Of the numerous approaches investigated, fusion of the encoded antigen to major histocompatibility complex class II-associated invariant chain (Ii) has been reported to enhance CD8(+) T-cell responses. We have previously shown that adenovirus vaccine encoding nonstructural (NS) hepatitis C virus (HCV) proteins induces potent T-cell responses in humans. However, even higher T-cell responses might be required to achieve efficacy against different HCV genotypes or therapeutic effect in chronically infected HCV patients. In this study, we assessed fusion of the HCV NS antigen to murine and human Ii expressed by the chimpanzee adenovirus vector ChAd3 or recombinant modified vaccinia Ankara in mice and nonhuman primates (NHPs). A dramatic increase was observed in outbred mice in which vaccination with ChAd3 expressing the fusion antigen resulted in a 10-fold increase in interferon-γ(+) CD8(+) T cells. In NHPs, CD8(+) T-cell responses were enhanced and accelerated with vectors encoding the Ii-fused antigen. These data show for the first time that the enhancement induced by vector vaccines encoding li-fused antigen was not species specific and can be translated from mice to NHPs, opening the way for testing in humans.
- Published
- 2014
- Full Text
- View/download PDF
61. Adenovirus Encoded Adjuvant (AdEnA) anti-CTLA-4, a novel strategy to improve Adenovirus based vaccines against infectious diseases and cancer.
- Author
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D'Alise AM, Nocchi L, Garzia I, Seclì L, Infante L, Troise F, Cotugno G, Allocca S, Romano G, Lahm A, Leoni G, Sasso E, Scarselli E, and Nicosia A
- Subjects
- Mice, Animals, Humans, Adenoviridae genetics, COVID-19 Vaccines, Adjuvants, Immunologic, Adjuvants, Pharmaceutic, Adenovirus Vaccines, COVID-19, Adenoviridae Infections, Communicable Diseases, Neoplasms
- Abstract
Introduction: Virus vectored genetic vaccines (Vvgv) represent a promising approach for eliciting immune protection against infectious diseases and cancer. However, at variance with classical vaccines to date, no adjuvant has been combined with clinically approved genetic vaccines, possibly due to the detrimental effect of the adjuvant-induced innate response on the expression driven by the genetic vaccine vector. We reasoned that a potential novel approach to develop adjuvants for genetic vaccines would be to "synchronize" in time and space the activity of the adjuvant with that of the vaccine., Methods: To this aim, we generated an Adenovirus vector encoding a murine anti-CTLA-4 monoclonal antibody (Ad-9D9) as a genetic adjuvant for Adenovirus based vaccines., Results: The co-delivery of Ad-9D9 with an Adeno-based COVID-19 vaccine encoding the Spike protein resulted in stronger cellular and humoral immune responses. In contrast, only a modest adjuvant effect was achieved when combining the vaccine with the same anti-CTLA-4 in its proteinaceous form. Importantly, the administration of the adjuvant vector at different sites of the vaccine vector abrogates the immunostimulatory effect. We showed that the adjuvant activity of Ad-α-CTLA-4 is independent from the vaccine antigen as it improved the immune response and efficacy of an Adenovirus based polyepitope vaccine encoding tumor neoantigens., Discussion: Our study demonstrated that the combination of Adenovirus Encoded Adjuvant (AdEnA) with an Adeno-encoded antigen vaccine enhances immune responses to viral and tumor antigens, representing a potent approach to develop more effective genetic vaccines., Competing Interests: ESc and AN are founders of Nouscom. Authors AMD’A, LN, IG, LS, LI, FT, GC, SA, GR, AL, and GL were employed by Nouscom. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 D’Alise, Nocchi, Garzia, Seclì, Infante, Troise, Cotugno, Allocca, Romano, Lahm, Leoni, Sasso, Scarselli and Nicosia.)
- Published
- 2023
- Full Text
- View/download PDF
62. Vector Aided Microenvironment programming (VAMP): reprogramming the TME with MVA virus expressing IL-12 for effective antitumor activity.
- Author
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Seclì L, Infante L, Nocchi L, De Lucia M, Cotugno G, Leoni G, Micarelli E, Garzia I, Avalle L, Sdruscia G, Troise F, Allocca S, Romano G, Scarselli E, and D'Alise AM
- Subjects
- Humans, Mice, Animals, Tumor Microenvironment, Vaccinia virus genetics, Cytokines metabolism, Interleukin-12 genetics, Interleukin-12 pharmacology, Neoplasms pathology
- Abstract
Background: Tumor microenvironment (TME) represents a critical hurdle in cancer immunotherapy, given its ability to suppress antitumor immunity. Several efforts are made to overcome this hostile TME with the development of new therapeutic strategies modifying TME to boost antitumor immunity. Among these, cytokine-based approaches have been pursued for their known immunomodulatory effects on different cell populations within the TME. IL-12 is a potent pro-inflammatory cytokine that demonstrates striking immune activation and tumor control but causes severe adverse effects when systemically administered. Thus, local administration is considered a potential strategy to achieve high cytokine concentrations at the tumor site while sparing systemic adverse effects., Methods: Modified Vaccinia Ankara (MVA) vector is a potent inducer of pro-inflammatory response. Here, we cloned IL-12 into the genome of MVA for intratumoral immunotherapy, combining the immunomodulatory properties of both the vector and the cargo. The antitumor activity of MVA-IL-12 and its effect on TME reprogramming were investigated in preclinical tumor models. RNA sequencing (RNA-Seq) analysis was performed to assess changes in the TME in treated and distal tumors and the effect on the intratumoral T-cell receptor repertoire., Results: Intratumoral injection of MVA-IL-12 resulted in strong antitumor activity with the complete remission of established tumors in multiple murine models, including those resistant to checkpoint inhibitors. The therapeutic activity of MVA-IL-12 was associated with very low levels of circulating cytokine. Effective TME reprogramming was demonstrated on treatment, with the reduction of immunosuppressive M2 macrophages while increasing pro-inflammatory M1, and recruitment of dendritic cells. TME switch from immunosuppressive into immunostimulatory environment allowed for CD8 T cells priming and expansion leading to tumor attack., Conclusions: Intratumoral administration of MVA-IL-12 turns immunologically 'cold' tumors 'hot' and overcomes resistance to programmed cell death protein-1 blockade., Competing Interests: Competing interests: ES is founder of Nouscom. AMD, LS, LI, LN, MDL, GC, GL, EM, IG, GS, FT, SA, GR are employees of Nouscom., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2023
- Full Text
- View/download PDF
63. Adenoviral-based vaccine promotes neoantigen-specific CD8 + T cell stemness and tumor rejection.
- Author
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D'Alise AM, Brasu N, De Intinis C, Leoni G, Russo V, Langone F, Baev D, Micarelli E, Petiti L, Picelli S, Fakih M, Le DT, Overman MJ, Shields AF, Pedersen KS, Shah MA, Mukherjee S, Faivre T, Delaite P, Scarselli E, and Pace L
- Subjects
- Adenoviridae, Animals, Antigens, Neoplasm metabolism, Humans, Mice, Receptors, Antigen, T-Cell metabolism, CD8-Positive T-Lymphocytes, Neoplasms metabolism
- Abstract
Upon chronic antigen exposure, CD8
+ T cells become exhausted, acquiring a dysfunctional state correlated with the inability to control infection or tumor progression. In contrast, stem-like CD8+ T progenitors maintain the ability to promote and sustain effective immunity. Adenovirus (Ad)-vectored vaccines encoding tumor neoantigens have been shown to eradicate large tumors when combined with anti-programmed cell death protein 1 (αPD-1) in murine models; however, the mechanisms and translational potential have not yet been elucidated. Here, we show that gorilla Ad vaccine targeting tumor neoepitopes enhances responses to αPD-1 therapy by improving immunogenicity and antitumor efficacy. Single-cell RNA sequencing demonstrated that the combination of Ad vaccine and αPD-1 increased the number of murine polyfunctional neoantigen-specific CD8+ T cells over αPD-1 monotherapy, with an accumulation of Tcf1+ stem-like progenitors in draining lymph nodes and effector CD8+ T cells in tumors. Combined T cell receptor (TCR) sequencing analysis highlighted a broader spectrum of neoantigen-specific CD8+ T cells upon vaccination compared to αPD-1 monotherapy. The translational relevance of these data is supported by results obtained in the first 12 patients with metastatic deficient mismatch repair (dMMR) tumors vaccinated with an Ad vaccine encoding shared neoantigens. Expansion and diversification of TCRs were observed in post-treatment biopsies of patients with clinical response, as well as an increase in tumor-infiltrating T cells with an effector memory signature. These findings indicate a promising mechanism to overcome resistance to PD-1 blockade by promoting immunogenicity and broadening the spectrum and magnitude of neoantigen-specific T cells infiltrating tumors.- Published
- 2022
- Full Text
- View/download PDF
64. Retargeted and Multi-cytokine-Armed Herpes Virus Is a Potent Cancer Endovaccine for Local and Systemic Anti-tumor Treatment.
- Author
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De Lucia M, Cotugno G, Bignone V, Garzia I, Nocchi L, Langone F, Petrovic B, Sasso E, Pepe S, Froechlich G, Gentile C, Zambrano N, Campadelli-Fiume G, Nicosia A, Scarselli E, and D'Alise AM
- Abstract
Oncolytic viruses (OVs) are novel anti-tumor agents with the ability to selectively infect and kill tumor cells while sparing normal tissue. Beyond tumor cytolysis, OVs are capable of priming an anti-tumor immune response via lysis and cross-presentation of locally expressed endogenous tumor antigens, acting as an "endovaccine." The effectiveness of OVs, similar to other immunotherapies, can be hampered by an immunosuppressive tumor microenvironment. In this study, we modified a previously generated oncolytic herpes simplex virus (oHSV) retargeted to the human HER2 (hHER2) tumor molecule and encoding murine interleukin-12 (mIL-12), by insertion of a second immunomodulatory molecule, murine granulocyte-macrophage colony-stimulating factor (mGM-CSF), to maximize therapeutic efficacy. We assessed the efficacy of this double-armed virus (R-123) compared to singly expressing GM-CSF and IL-12 oHSVs in tumor-bearing mice. While monotherapies were poorly effective, combination with α-PD1 enhanced the anti-tumor response, with the highest efficacy of 100% response rate achieved by the combination of R-123 and α-PD1. Efficacy was T cell-dependent, and the induced immunity was long lasting and able to reject a second contralateral tumor. Importantly, systemic delivery of R-123 combined with α-PD1 was effective in inhibiting the development of tumor metastasis. As such, this approach could have a significant therapeutic impact paving the way for further development of this platform in cancer immunotherapy., (© 2020 The Author(s).)
- Published
- 2020
- Full Text
- View/download PDF
65. MHC class II invariant chain-adjuvanted viral vectored vaccines enhances T cell responses in humans.
- Author
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Esposito I, Cicconi P, D'Alise AM, Brown A, Esposito M, Swadling L, Holst PJ, Bassi MR, Stornaiuolo M, Mori F, Vassilev V, Li W, Donnison T, Gentile C, Turner B, von Delft A, Del Sorbo M, Barra F, Contino AM, Abbate A, Novellino E, Thomsen AR, Christensen JP, Lahm A, Grazioli F, Ammendola V, Siani L, Colloca S, Klenerman P, Nicosia A, Dorrell L, Folgori A, Capone S, and Barnes E
- Subjects
- Antigens, Differentiation, B-Lymphocyte genetics, CD8-Positive T-Lymphocytes, Hepacivirus genetics, Histocompatibility Antigens Class II, Humans, Viral Vaccines
- Abstract
Strategies to enhance the induction of high magnitude T cell responses through vaccination are urgently needed. Major histocompatibility complex (MHC) class II-associated invariant chain (Ii) plays a critical role in antigen presentation, forming MHC class II peptide complexes for the generation of CD4
+ T cell responses. Preclinical studies evaluating the fusion of Ii to antigens encoded in vector delivery systems have shown that this strategy may enhance T cell immune responses to the encoded antigen. We now assess this strategy in humans, using chimpanzee adenovirus 3 and modified vaccinia Ankara vectors encoding human Ii fused to the nonstructural (NS) antigens of hepatitis C virus (HCV) in a heterologous prime/boost regimen. Vaccination was well tolerated and enhanced the peak magnitude, breadth, and proliferative capacity of anti-HCV T cell responses compared to non-Ii vaccines in humans. Very high frequencies of HCV-specific T cells were elicited in humans. Polyfunctional HCV-specific CD8+ and CD4+ responses were induced with up to 30% of CD3+ CD8+ cells targeting single HCV epitopes; these were mostly effector memory cells with a high proportion expressing T cell activation and cytolytic markers. No volunteers developed anti-Ii T cell or antibody responses. Using a mouse model and in vitro experiments, we show that Ii fused to NS increases HCV immune responses through enhanced ubiquitination and proteasomal degradation. This strategy could be used to develop more potent HCV vaccines that may contribute to the HCV elimination targets and paves the way for developing class II Ii vaccines against cancer and other infections., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)- Published
- 2020
- Full Text
- View/download PDF
66. Mucosal delivery of a vectored RSV vaccine is safe and elicits protective immunity in rodents and nonhuman primates.
- Author
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Pierantoni A, Esposito ML, Ammendola V, Napolitano F, Grazioli F, Abbate A, Del Sorbo M, Siani L, D'Alise AM, Taglioni A, Perretta G, Siccardi A, Soprana E, Panigada M, Thom M, Scarselli E, Folgori A, Colloca S, Taylor G, Cortese R, Nicosia A, Capone S, and Vitelli A
- Abstract
Respiratory Syncytial Virus (RSV) is a leading cause of severe respiratory disease in infants and the elderly. No vaccine is presently available to address this major unmet medical need. We generated a new genetic vaccine based on chimpanzee Adenovirus (PanAd3-RSV) and Modified Vaccinia Ankara RSV (MVA-RSV) encoding the F, N, and M2-1 proteins of RSV, for the induction of neutralizing antibodies and broad cellular immunity. Because RSV infection is restricted to the respiratory tract, we compared intranasal (IN) and intramuscular (M) administration for safety, immunogenicity, and efficacy in different species. A single IN or IM vaccination completely protected BALB/c mice and cotton rats against RSV replication in the lungs. However, only IN administration could prevent infection in the upper respiratory tract. IM vaccination with MVA-RSV also protected cotton rats from lower respiratory tract infection in the absence of detectable neutralizing antibodies. Heterologous prime boost with PanAd3-RSV and MVA-RSV elicited high neutralizing antibody titers and broad T-cell responses in nonhuman primates. In addition, animals primed in the nose developed mucosal IgA against the F protein. In conclusion, we have shown that our vectored RSV vaccine induces potent cellular and humoral responses in a primate model, providing strong support for clinical testing.
- Published
- 2015
- Full Text
- View/download PDF
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