Novel peptide-based oncolytic vaccine for enhancement of adaptive antitumor immune response via co-engagement of innate Fcγ and Fcα receptors
Background Cancer immunotherapy relies on using the immune system to recognize and eradicate cancer cells. Adaptive immunity, which consists of mainly antigen-specific cytotoxic T cells, plays a pivotal role in controlling cancer progression. However, innate immunity is a necessary component of the...
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2024-03-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/12/3/e008342.full |
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| author | Sari Pesonen Sara Feola Manlio Fusciello Vincenzo Cerullo Firas Hamdan Jacopo Chiaro Michaela Feodoroff Gabriella Antignani Salvatore Russo Jeanette Leusen Mikaela Grönholm Federica D'Alessio Riikka Mölsä Virpi Stigzelius Paolo Bottega |
| author_facet | Sari Pesonen Sara Feola Manlio Fusciello Vincenzo Cerullo Firas Hamdan Jacopo Chiaro Michaela Feodoroff Gabriella Antignani Salvatore Russo Jeanette Leusen Mikaela Grönholm Federica D'Alessio Riikka Mölsä Virpi Stigzelius Paolo Bottega |
| author_sort | Sari Pesonen |
| collection | DOAJ |
| description | Background Cancer immunotherapy relies on using the immune system to recognize and eradicate cancer cells. Adaptive immunity, which consists of mainly antigen-specific cytotoxic T cells, plays a pivotal role in controlling cancer progression. However, innate immunity is a necessary component of the cancer immune response to support an immunomodulatory state, enabling T-cell immunosurveillance.Methods Here, we elucidated and exploited innate immune cells to sustain the generation of antigen-specific T cells on the use of our cancer vaccine platform. We explored a previously developed oncolytic adenovirus (AdCab) encoding for a PD-L1 (Programmed-Death Ligand 1) checkpoint inhibitor, which consists of a PD-1 (Programmed Cell Death Protein 1) ectodomain fused to an IgG/A cross-hybrid Fc. We coated AdCab with major histocompatibility complex (MHC-I)-restricted tumor peptides, generating a vaccine platform (named PeptiCab); the latter takes advantage of viral immunogenicity, peptide cancer specificity to prime T-cell responses, and antibody-mediated effector functions.Results As proof of concept, PeptiCab was used in murine models of melanoma and colon cancer, resulting in tumor growth control and generation of systemic T-cell-mediated antitumor responses. In specific, PeptiCab was able to generate antitumor T effector memory cells able to secrete various inflammatory cytokines. Moreover, PeptiCab was able to polarize neutrophils to attain an antigen-presenting phenotype by upregulating MHC-II, CD80 and CD86 resulting in an enhanced T-cell expansion.Conclusion Our data suggest that exploiting innate immunity activates T-cell antitumor responses, enhancing the efficiency of a vaccine platform based on oncolytic adenovirus coated with MHC-I-restricted tumor peptides. |
| format | Article |
| id | doaj-art-0b92fefeeea843e8b25b72efaf0979c0 |
| institution | Kabale University |
| issn | 2051-1426 |
| language | English |
| publishDate | 2024-03-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-0b92fefeeea843e8b25b72efaf0979c02024-12-18T01:15:10ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262024-03-0112310.1136/jitc-2023-008342Novel peptide-based oncolytic vaccine for enhancement of adaptive antitumor immune response via co-engagement of innate Fcγ and Fcα receptorsSari Pesonen0Sara Feola1Manlio Fusciello2Vincenzo Cerullo3Firas Hamdan4Jacopo Chiaro5Michaela Feodoroff6Gabriella Antignani7Salvatore Russo8Jeanette Leusen9Mikaela Grönholm10Federica D'Alessio11Riikka Mölsä12Virpi Stigzelius13Paolo Bottega14Valo Therapeutics Oy, Helsinki, FinlandUniversity of Helsinki Faculty of Pharmacy, Laboratory of Immunovirotherapy, Drug Research Program Helsinki, Uusimaa, FI, Helsinki, FinlandUniversity of Helsinki Faculty of Pharmacy, Laboratory of Immunovirotherapy, Drug Research Program Helsinki, Uusimaa, FI, Helsinki, FinlandUniversity of Helsinki Faculty of Pharmacy, Laboratory of Immunovirotherapy, Drug Research Program Helsinki, Uusimaa, FI, Helsinki, FinlandLaboratory of Immunovirotherapy, Drug Research Program, Faculty of Pharmacy, University of Helsinki, Helsinki, FinlandUniversity of Helsinki Faculty of Pharmacy, Laboratory of Immunovirotherapy, Drug Research Program Helsinki, Uusimaa, FI, Helsinki, FinlandUniversity of Helsinki Faculty of Pharmacy, Laboratory of Immunovirotherapy, Drug Research Program Helsinki, Uusimaa, FI, Helsinki, FinlandUniversity of Helsinki Faculty of Pharmacy, Laboratory of Immunovirotherapy, Drug Research Program Helsinki, Uusimaa, FI, Helsinki, FinlandUniversity of Helsinki Faculty of Pharmacy, Laboratory of Immunovirotherapy, Drug Research Program Helsinki, Uusimaa, FI, Helsinki, FinlandCenter for Translational Immunology, UMC Utrecht, Utrecht, The NetherlandsUniversity of Helsinki Faculty of Pharmacy, Laboratory of Immunovirotherapy, Drug Research Program Helsinki, Uusimaa, FI, Helsinki, FinlandHelsinki Institute of Life Science (HiLIFE), Fabianinkatu 33, University of Helsinki, 00710 Helsinki, Finland, Helsinki, FinlandUniversity of Helsinki Faculty of Pharmacy, Laboratory of Immunovirotherapy, Drug Research Program Helsinki, Uusimaa, FI, Helsinki, FinlandUniversity of Helsinki Faculty of Pharmacy, Laboratory of Immunovirotherapy, Drug Research Program Helsinki, Uusimaa, FI, Helsinki, FinlandUniversity of Helsinki Faculty of Pharmacy, Laboratory of Immunovirotherapy, Drug Research Program Helsinki, Uusimaa, FI, Helsinki, FinlandBackground Cancer immunotherapy relies on using the immune system to recognize and eradicate cancer cells. Adaptive immunity, which consists of mainly antigen-specific cytotoxic T cells, plays a pivotal role in controlling cancer progression. However, innate immunity is a necessary component of the cancer immune response to support an immunomodulatory state, enabling T-cell immunosurveillance.Methods Here, we elucidated and exploited innate immune cells to sustain the generation of antigen-specific T cells on the use of our cancer vaccine platform. We explored a previously developed oncolytic adenovirus (AdCab) encoding for a PD-L1 (Programmed-Death Ligand 1) checkpoint inhibitor, which consists of a PD-1 (Programmed Cell Death Protein 1) ectodomain fused to an IgG/A cross-hybrid Fc. We coated AdCab with major histocompatibility complex (MHC-I)-restricted tumor peptides, generating a vaccine platform (named PeptiCab); the latter takes advantage of viral immunogenicity, peptide cancer specificity to prime T-cell responses, and antibody-mediated effector functions.Results As proof of concept, PeptiCab was used in murine models of melanoma and colon cancer, resulting in tumor growth control and generation of systemic T-cell-mediated antitumor responses. In specific, PeptiCab was able to generate antitumor T effector memory cells able to secrete various inflammatory cytokines. Moreover, PeptiCab was able to polarize neutrophils to attain an antigen-presenting phenotype by upregulating MHC-II, CD80 and CD86 resulting in an enhanced T-cell expansion.Conclusion Our data suggest that exploiting innate immunity activates T-cell antitumor responses, enhancing the efficiency of a vaccine platform based on oncolytic adenovirus coated with MHC-I-restricted tumor peptides.https://jitc.bmj.com/content/12/3/e008342.full |
| spellingShingle | Sari Pesonen Sara Feola Manlio Fusciello Vincenzo Cerullo Firas Hamdan Jacopo Chiaro Michaela Feodoroff Gabriella Antignani Salvatore Russo Jeanette Leusen Mikaela Grönholm Federica D'Alessio Riikka Mölsä Virpi Stigzelius Paolo Bottega Novel peptide-based oncolytic vaccine for enhancement of adaptive antitumor immune response via co-engagement of innate Fcγ and Fcα receptors Journal for ImmunoTherapy of Cancer |
| title | Novel peptide-based oncolytic vaccine for enhancement of adaptive antitumor immune response via co-engagement of innate Fcγ and Fcα receptors |
| title_full | Novel peptide-based oncolytic vaccine for enhancement of adaptive antitumor immune response via co-engagement of innate Fcγ and Fcα receptors |
| title_fullStr | Novel peptide-based oncolytic vaccine for enhancement of adaptive antitumor immune response via co-engagement of innate Fcγ and Fcα receptors |
| title_full_unstemmed | Novel peptide-based oncolytic vaccine for enhancement of adaptive antitumor immune response via co-engagement of innate Fcγ and Fcα receptors |
| title_short | Novel peptide-based oncolytic vaccine for enhancement of adaptive antitumor immune response via co-engagement of innate Fcγ and Fcα receptors |
| title_sort | novel peptide based oncolytic vaccine for enhancement of adaptive antitumor immune response via co engagement of innate fcγ and fcα receptors |
| url | https://jitc.bmj.com/content/12/3/e008342.full |
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