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.

• Authors: Ricardo G Alvim, Petrina Georgala, Lucas Nogueira, Alexander J Somma, Karan Nagar, Jasmine Thomas, Laura Alvim, Amelia Riegel, Christopher Hughes, Jie Chen, Augusto B Reis, Souhil Lebdai, Avigdor Scherz, Steven Zanganeh, Rui Gardner, Kwanghee Kim, Jonathan A Coleman
• Journal: Molecules (Basel, Switzerland) (Molecules) Vol. 26 Issue 12 (06 19 2021) ISSN: 1420-3049 [Electronic] Switzerland
• PMID: 34205347 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Immune Checkpoint Inhibitors
• PDCD1 protein, human
• Programmed Cell Death 1 Receptor
• Receptors, OX40
• TNFRSF4 protein, human

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Disease Models, Animal
• Humans
• Immune Checkpoint Inhibitors (pharmacology)
• Immunity (drug effects)
• Immunotherapy (methods)
• Male
• Mice
• Mice, Inbred C57BL
• Photochemotherapy (methods)
• Programmed Cell Death 1 Receptor (agonists)
• Receptors, OX40 (agonists)
• T-Lymphocytes (drug effects)
• Urologic Neoplasms (immunology, metabolism, therapy)
• Xenograft Model Antitumor Assays (methods)