Potentiation of immunomodulatory antibody therapy with oncolytic viruses for treatment of cancer
Identification of the immune suppressive mechanisms active within the tumor microenvironment led to development of immunotherapeutic strategies aiming to reverse the immunosuppression and to enhance the function of tumor-infiltrating lymphocytes. Of those, cancer therapy with antibodies targeting th...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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Elsevier
2014-01-01
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| Series: | Molecular Therapy: Oncolytics |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2372770516300262 |
| _version_ | 1818530742370566144 |
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| author | Dmitriy Zamarin Jedd D Wolchok |
| author_facet | Dmitriy Zamarin Jedd D Wolchok |
| author_sort | Dmitriy Zamarin |
| collection | DOAJ |
| description | Identification of the immune suppressive mechanisms active within the tumor microenvironment led to development of immunotherapeutic strategies aiming to reverse the immunosuppression and to enhance the function of tumor-infiltrating lymphocytes. Of those, cancer therapy with antibodies targeting the immune costimulatory and coinhibitory receptors has demonstrated significant promise in the recent years, with multiple antibodies entering clinical testing. The responses to these agents, however, have not been universal and have not been observed in all cancer types, calling for identification of appropriate predictive biomarkers and development of combinatorial strategies. Pre-existing immune infiltration in tumors has been demonstrated to have a strong association with response to immunotherapies, with the type I interferon (IFN) pathway emerging as a key player in tumor innate immune recognition and activation of adaptive immunity. These findings provide a rationale for evaluation of strategies targeting the type I IFN pathway as a means to enhance tumor immune recognition and infiltration, which could potentially make them susceptible to therapeutics targeting the cosignaling receptors. To this end in particular, oncolytic viruses (OVs) have been demonstrated to enhance tumor recognition by the immune system through multiple mechanisms, which include upregulation of major histocompatibility complex and costimulatory molecules on cancer cells, immunogenic cell death and antigen release, and activation of the type I IFN pathway. Evidence is now emerging that combination therapies using OVs and agents targeting immune cosignaling receptors such as 4-1BB, PD-1, and CTLA-4 may work in concert to enhance antitumor immunity and therapeutic efficacy. Our evolving understanding of the interplay between OVs and the immune system demonstrates that the virus-induced antitumor immune responses can be harnessed to drive the efficacy of the agents targeting cosignaling receptors and provides a strong rationale for integration of such therapies in clinic. |
| first_indexed | 2024-12-11T17:23:33Z |
| format | Article |
| id | doaj.art-a2052a063f784f0d8b75d50aed66156e |
| institution | Directory Open Access Journal |
| issn | 2372-7705 |
| language | English |
| last_indexed | 2024-12-11T17:23:33Z |
| publishDate | 2014-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Oncolytics |
| spelling | doaj.art-a2052a063f784f0d8b75d50aed66156e2022-12-22T00:57:02ZengElsevierMolecular Therapy: Oncolytics2372-77052014-01-011C10.1038/mto.2014.4Potentiation of immunomodulatory antibody therapy with oncolytic viruses for treatment of cancerDmitriy Zamarin0Jedd D Wolchok1Swim Across America Laboratory, Immunology Program, Sloan-Kettering Institute for Cancer Research, New York, New York, USASwim Across America Laboratory, Immunology Program, Sloan-Kettering Institute for Cancer Research, New York, New York, USAIdentification of the immune suppressive mechanisms active within the tumor microenvironment led to development of immunotherapeutic strategies aiming to reverse the immunosuppression and to enhance the function of tumor-infiltrating lymphocytes. Of those, cancer therapy with antibodies targeting the immune costimulatory and coinhibitory receptors has demonstrated significant promise in the recent years, with multiple antibodies entering clinical testing. The responses to these agents, however, have not been universal and have not been observed in all cancer types, calling for identification of appropriate predictive biomarkers and development of combinatorial strategies. Pre-existing immune infiltration in tumors has been demonstrated to have a strong association with response to immunotherapies, with the type I interferon (IFN) pathway emerging as a key player in tumor innate immune recognition and activation of adaptive immunity. These findings provide a rationale for evaluation of strategies targeting the type I IFN pathway as a means to enhance tumor immune recognition and infiltration, which could potentially make them susceptible to therapeutics targeting the cosignaling receptors. To this end in particular, oncolytic viruses (OVs) have been demonstrated to enhance tumor recognition by the immune system through multiple mechanisms, which include upregulation of major histocompatibility complex and costimulatory molecules on cancer cells, immunogenic cell death and antigen release, and activation of the type I IFN pathway. Evidence is now emerging that combination therapies using OVs and agents targeting immune cosignaling receptors such as 4-1BB, PD-1, and CTLA-4 may work in concert to enhance antitumor immunity and therapeutic efficacy. Our evolving understanding of the interplay between OVs and the immune system demonstrates that the virus-induced antitumor immune responses can be harnessed to drive the efficacy of the agents targeting cosignaling receptors and provides a strong rationale for integration of such therapies in clinic.http://www.sciencedirect.com/science/article/pii/S2372770516300262 |
| spellingShingle | Dmitriy Zamarin Jedd D Wolchok Potentiation of immunomodulatory antibody therapy with oncolytic viruses for treatment of cancer Molecular Therapy: Oncolytics |
| title | Potentiation of immunomodulatory antibody therapy with oncolytic viruses for treatment of cancer |
| title_full | Potentiation of immunomodulatory antibody therapy with oncolytic viruses for treatment of cancer |
| title_fullStr | Potentiation of immunomodulatory antibody therapy with oncolytic viruses for treatment of cancer |
| title_full_unstemmed | Potentiation of immunomodulatory antibody therapy with oncolytic viruses for treatment of cancer |
| title_short | Potentiation of immunomodulatory antibody therapy with oncolytic viruses for treatment of cancer |
| title_sort | potentiation of immunomodulatory antibody therapy with oncolytic viruses for treatment of cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2372770516300262 |
| work_keys_str_mv | AT dmitriyzamarin potentiationofimmunomodulatoryantibodytherapywithoncolyticvirusesfortreatmentofcancer AT jedddwolchok potentiationofimmunomodulatoryantibodytherapywithoncolyticvirusesfortreatmentofcancer |