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Título

COMBINED OX40 AGONIST AND PD-1 INHIBITOR IMMUNOTHERAPY IMPROVES THE EFFICACY OF VASCULAR TARGETED PHOTODYNAMIC THERAPY IN A UROTHELIAL TUMOR MODEL

Introdução, Material, Método, Resultados, Discussão e Conclusões

Purpose: Vascular targeted photodynamic therapy (VTP) is a non-surgical tumor ablation approach used to treat early-stage prostate cancer and may also be effective for upper tract urothelial cancer (UTUC) based on preclinical data. Toward increasing response rates to VTP, we evaluated its efficacy in combination with concurrent PD-1 inhibitor/OX40 agonist immunotherapy in a urothelial tumor-bearing model.

Material and Methods: In mice allografted with MB-49 UTUC cells, we compared the effects of combined VTP with PD-1 inhibitor/OX40 agonist with those of the component treatments on tumor growth, survival, lung metastasis, and antitumor immune responses.

Results: The combination of VTP with both PD-1 inhibitor and OX40 agonist inhibited tumor growth and metastasis and prolonged survival to a much greater degree than VTP with either immunotherapeutic individually. These effects result from increased tumor infiltration and intratumoral proliferation of cytotoxic and helper T cells, depletion of Treg cells, and suppression of myeloid-derived suppressor cells.

Conclusions: Our findings suggest that VTP synergizes with PD-1 blockade and OX40 agonist to promote strong antitumor immune responses, yielding therapeutic efficacy in an animal model of urothelial cancer.

Palavras Chave

bladder cancer, tumor ablation, TOOKAD, focal therapy, immunotherapy

Área

Câncer Bexiga

Instituições

MSKCC - - Estados Unidos

Autores

RICARDO ALVIM, LUCAS NOGUEIRA NOGUEIRA, PETRINA GEORGALA, KARAN NAGAR, JASMINE THOMAS, LAURA ALVIM, AVIGDOR SCHERZ, ANDREW TRACEY, Kwanghee Kim, JONATHAN COLEMAN