Combined OX40 Agonist and PD-1 Inhibitor Immunotherapy Improves the Efficacy of Vascular Targeted Photodynamic Therapy in a Urothelial Tumor Model

Molecules

Steven Zanganeh¹  Petrina Georgala²  Avigdor Scherz³  Augusto B. Reis⁴  Rui Gardner⁵  Ricardo G. Alvim⁶  Jie Chen⁶  Lucas Nogueira⁶  Kwanghee Kim⁶  Alexander J. Somma⁶  Karan Nagar⁶  Jasmine Thomas⁶  Souhil Lebdai⁶  Jonathan A. Coleman⁶  Laura Alvim⁶  Amelia Riegel⁶  Christopher Hughes⁶ 

[1] Department of Bioengineering, University of Massachusetts, Dartmouth, MA 02747, USA;Department of Neurosurgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA;Department of Plants and Environmental Sciences, The Weizmann Institute of Science, Rehovot 76100, Israel;Department of Surgery, Federal University of Minas Gerais, Belo Horizonte 30130-100, Brazil;Flow Cytometry Core Facility, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA;Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA;

关键词: bladder cancer;    tumor ablation;    TOOKAD;    focal therapy;    immunotherapy;   

DOI  :  10.3390/molecules26123744

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown