Combinatorial approaches with vascular photodynamic therapy with redaporfin and immune checkpoint blockers (Conference Presentation)

Ana Catarina Sousa Lobo; Lígia C. Gomes-da-Silva; Luis G. Arnaut

doi:10.1117/12.2526034

14 August 2019 Combinatorial approaches with vascular photodynamic therapy with redaporfin and immune checkpoint blockers (Conference Presentation)

Ana Catarina Sousa Lobo, Lígia C. Gomes-da-Silva, Luis G. Arnaut

Author Affiliations +

Proceedings Volume 11070, 17th International Photodynamic Association World Congress; 1107036 (2019) https://doi.org/10.1117/12.2526034
Event: 17th International Photodynamic Association World Congress, 2019, Cambridge, Massachusetts, United States

Abstract

Vascular photodynamic therapy (PDT) with redaporfin was shown to destroy the primary tumor and to reduce the development of distant cancer lesions in animal models, thus suggesting anti-tumor immunity. Vascular-PDT with redaporfin triggers an acute local inflammation, neutrophilia and leads to an increase in CD4+/CD8+ T cells ratio, which has been correlated with increased survival rates in cancer patients, and further corroborates the activation of the adaptive immune system a few hours post-PDT. Previous experiments also confirmed the importance of some cell populations that are increased in response to PDT (CD4+ and CD8+ T cells expressing IFNγ,). Specific inhibition with monoclonal antibodies revealed significant decreases in percentage of survival of CD8+ T cells depleted animals, in comparison with PDT alone. To evaluate if combinatorial therapies in animal model would led to synergies between PDT and immunotherapy, we evaluated the therapeutic outcome of the combination between redaporfin-PDT and immune checkpoint blockers (ICB). ICB’s function as boosters of tumor immunity through reversing T-cell exhaustion and are an emerging immunotherapeutic modality. Our experiments with mice bearing CT26WT tumors revealed an improvement of redaporfin-PDT outcome when combined with anti-CTLA-4 antibody therapy, but no significant differences were observed with anti-PD-1. On-going experiments intend to clarify about the immune infiltrates variations in the tumor bed after combinatorial approaches, as well as to validate these results in a second animal model.

Conference Presentation

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Ana Catarina Sousa Lobo, Lígia C. Gomes-da-Silva, and Luis G. Arnaut "Combinatorial approaches with vascular photodynamic therapy with redaporfin and immune checkpoint blockers (Conference Presentation)", Proc. SPIE 11070, 17th International Photodynamic Association World Congress, 1107036 (14 August 2019); https://doi.org/10.1117/12.2526034

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KEYWORDS

Photodynamic therapy

Tumors

Animal model studies

Cancer

Therapeutics

Inflammation

Monoclonal antibodies

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