Combined OX40 agonist and PD-1 inhibitor immunotherapy improves the efficacy of vascular targeted photodynamic therapy in a urothelial tumor model Journal Article


Authors: Alvim, R. G.; Georgala, P.; Nogueira, L.; Somma, A. J.; Nagar, K.; Thomas, J.; Alvim, L.; Riegel, A.; Hughes, C.; Chen, J.; Reis, A. B.; Lebdai, S.; Scherz, A.; Zanganeh, S.; Gardner, R.; Kim, K.; Coleman, J. A.
Article Title: Combined OX40 agonist and PD-1 inhibitor immunotherapy improves the efficacy of vascular targeted photodynamic therapy in a urothelial tumor model
Abstract: Purpose: Vascular targeted photodynamic therapy (VTP) is a nonsurgical 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. Experimental design: 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 prolonged survival to a 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. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
Keywords: bladder cancer; immunotherapy; focal therapy; tumor ablation; tookad
Journal Title: Molecules
Volume: 26
Issue: 12
ISSN: 1420-3049
Publisher: MDPI  
Date Published: 2021-06-02
Start Page: 3744
Language: English
DOI: 10.3390/molecules26123744
PUBMED: 34205347
PROVIDER: scopus
PMCID: PMC8234268
DOI/URL:
Notes: Article -- Export Date: 2 August 2021 -- Source: Scopus
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