From Co-Stimulation to Co-Inhibition: A Continuum of Immunotherapy Care Toward Long-Term Survival in Melanoma
Elena Simonetti,1 Serena Cutarella,1 Monica Valente,2 Tommaso Sani,1 Matteo Ravara,1 Michele Maio,1– 3 Anna Maria Di Giacomo1– 3 1University of Siena, Siena, Italy; 2Center for Immuno-Oncology, Medical Oncology and Immunotherapy, Department of Oncology, University Hospital, Siena, Italy; 3NIBIT Foun...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2023-04-01
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| Series: | OncoTargets and Therapy |
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| Online Access: | https://www.dovepress.com/from-co-stimulation-to-co-inhibition-a-continuum-of-immunotherapy-care-peer-reviewed-fulltext-article-OTT |
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| author | Simonetti E Cutarella S Valente M Sani T Ravara M Maio M Di Giacomo AM |
| author_facet | Simonetti E Cutarella S Valente M Sani T Ravara M Maio M Di Giacomo AM |
| author_sort | Simonetti E |
| collection | DOAJ |
| description | Elena Simonetti,1 Serena Cutarella,1 Monica Valente,2 Tommaso Sani,1 Matteo Ravara,1 Michele Maio,1– 3 Anna Maria Di Giacomo1– 3 1University of Siena, Siena, Italy; 2Center for Immuno-Oncology, Medical Oncology and Immunotherapy, Department of Oncology, University Hospital, Siena, Italy; 3NIBIT Foundation Onlus, Genoa, ItalyCorrespondence: Anna Maria Di Giacomo, Center for Immuno-Oncology, Medical Oncology and Immunotherapy, Department of Oncology, University Hospital of Siena, Viale Bracci, 14, Siena, 53100, Italy, Email annamaria.digiacomo@unisi.itAbstract: Harnessing the immune system with immune-checkpoint(s) blockade (ICB) has dramatically changed the treatment landscape of advanced melanoma patients in the last decade. Indeed, durable clinical responses and long-term survival can be achieved with anti-Cytotoxic T-Lymphocyte Antigen-4 (CTLA-4) and anti-Programmed cell Death-1 (PD-1) monoclonal antibodies (mAb) either alone or in combination. Despite these unprecedented results, due to intrinsic or acquired resistance to ICB-based immunotherapy, about half of metastatic melanoma (MM) patients neither respond to therapy nor experience durable clinical benefit or long-term survival. To improve the efficacy of ICB therapy among a larger proportion of MM patients, in addition to the targeting of immune-checkpoint(s) inhibitors (ICI) such as CTLA-4 or PD-1, several co-stimulatory molecules, such as Inducible T-cell COStimulator (ICOS), CD137 and OX40, have been investigated in MM, with initial signs of activity. Thus, a number of MM patients have been exposed to co-inhibitory and co-stimulatory mAb in the course of their disease. Being aware of the clinical outcome of such patients may pave the way to novel and more effective clinical approaches and therapeutic sequences for MM patients. Here we report a paradigmatic clinical case of a cutaneous MM patient who achieved multiple and durable complete responses, leading to an extraordinary long-term survival with sequential ICB therapies, suggesting the possibility to build a highly effective continuum of care with co-inhibitory and co-stimulatory therapeutic mAb.Keywords: immunotherapy, combinations, anti-PD1, anti-CTLA-4, CD137 agonist, ICOS agonist |
| first_indexed | 2024-04-09T18:27:28Z |
| format | Article |
| id | doaj.art-4d388475e7be4f0eaa32ba3adba59b9a |
| institution | Directory Open Access Journal |
| issn | 1178-6930 |
| language | English |
| last_indexed | 2024-04-09T18:27:28Z |
| publishDate | 2023-04-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | OncoTargets and Therapy |
| spelling | doaj.art-4d388475e7be4f0eaa32ba3adba59b9a2023-04-11T19:05:00ZengDove Medical PressOncoTargets and Therapy1178-69302023-04-01Volume 1622723282820From Co-Stimulation to Co-Inhibition: A Continuum of Immunotherapy Care Toward Long-Term Survival in MelanomaSimonetti ECutarella SValente MSani TRavara MMaio MDi Giacomo AMElena Simonetti,1 Serena Cutarella,1 Monica Valente,2 Tommaso Sani,1 Matteo Ravara,1 Michele Maio,1– 3 Anna Maria Di Giacomo1– 3 1University of Siena, Siena, Italy; 2Center for Immuno-Oncology, Medical Oncology and Immunotherapy, Department of Oncology, University Hospital, Siena, Italy; 3NIBIT Foundation Onlus, Genoa, ItalyCorrespondence: Anna Maria Di Giacomo, Center for Immuno-Oncology, Medical Oncology and Immunotherapy, Department of Oncology, University Hospital of Siena, Viale Bracci, 14, Siena, 53100, Italy, Email annamaria.digiacomo@unisi.itAbstract: Harnessing the immune system with immune-checkpoint(s) blockade (ICB) has dramatically changed the treatment landscape of advanced melanoma patients in the last decade. Indeed, durable clinical responses and long-term survival can be achieved with anti-Cytotoxic T-Lymphocyte Antigen-4 (CTLA-4) and anti-Programmed cell Death-1 (PD-1) monoclonal antibodies (mAb) either alone or in combination. Despite these unprecedented results, due to intrinsic or acquired resistance to ICB-based immunotherapy, about half of metastatic melanoma (MM) patients neither respond to therapy nor experience durable clinical benefit or long-term survival. To improve the efficacy of ICB therapy among a larger proportion of MM patients, in addition to the targeting of immune-checkpoint(s) inhibitors (ICI) such as CTLA-4 or PD-1, several co-stimulatory molecules, such as Inducible T-cell COStimulator (ICOS), CD137 and OX40, have been investigated in MM, with initial signs of activity. Thus, a number of MM patients have been exposed to co-inhibitory and co-stimulatory mAb in the course of their disease. Being aware of the clinical outcome of such patients may pave the way to novel and more effective clinical approaches and therapeutic sequences for MM patients. Here we report a paradigmatic clinical case of a cutaneous MM patient who achieved multiple and durable complete responses, leading to an extraordinary long-term survival with sequential ICB therapies, suggesting the possibility to build a highly effective continuum of care with co-inhibitory and co-stimulatory therapeutic mAb.Keywords: immunotherapy, combinations, anti-PD1, anti-CTLA-4, CD137 agonist, ICOS agonisthttps://www.dovepress.com/from-co-stimulation-to-co-inhibition-a-continuum-of-immunotherapy-care-peer-reviewed-fulltext-article-OTTimmunotherapycombinationsanti-pd1anti-ctla-4cd137 agonisticos agonist |
| spellingShingle | Simonetti E Cutarella S Valente M Sani T Ravara M Maio M Di Giacomo AM From Co-Stimulation to Co-Inhibition: A Continuum of Immunotherapy Care Toward Long-Term Survival in Melanoma OncoTargets and Therapy immunotherapy combinations anti-pd1 anti-ctla-4 cd137 agonist icos agonist |
| title | From Co-Stimulation to Co-Inhibition: A Continuum of Immunotherapy Care Toward Long-Term Survival in Melanoma |
| title_full | From Co-Stimulation to Co-Inhibition: A Continuum of Immunotherapy Care Toward Long-Term Survival in Melanoma |
| title_fullStr | From Co-Stimulation to Co-Inhibition: A Continuum of Immunotherapy Care Toward Long-Term Survival in Melanoma |
| title_full_unstemmed | From Co-Stimulation to Co-Inhibition: A Continuum of Immunotherapy Care Toward Long-Term Survival in Melanoma |
| title_short | From Co-Stimulation to Co-Inhibition: A Continuum of Immunotherapy Care Toward Long-Term Survival in Melanoma |
| title_sort | from co stimulation to co inhibition a continuum of immunotherapy care toward long term survival in melanoma |
| topic | immunotherapy combinations anti-pd1 anti-ctla-4 cd137 agonist icos agonist |
| url | https://www.dovepress.com/from-co-stimulation-to-co-inhibition-a-continuum-of-immunotherapy-care-peer-reviewed-fulltext-article-OTT |
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