Enhanced potency of immune checkpoint inhibitors against poorly immunological solid tumors by immune stimulatory oncolytic adenoviruses-mediated remodeling of the tumor microenvironment
Hyo Min Ahn, Bo-Kyeong Jung, JinWoo Hong, Dayoung Hong, A-Rum Yoon, Chae-Ok Yun
TL;DR
Researchers found that combining immune checkpoint inhibitors with oncolytic adenoviruses can boost immune responses against tumors that are typically hard to treat.
Contribution
The study identifies αPD-1 as the optimal immune checkpoint inhibitor to synergize with oncolytic adenoviruses for treating poorly immunological solid tumors.
Findings
Combining αPD-1 with oncolytic adenoviruses enhances antitumor immune responses.
Oncolytic adenoviruses expressing IL-12 and other factors help overcome tumor immunosuppression.
The synergy between αPD-1 and oncolytic Ads is effective against non-immunogenic solid tumors.
Abstract
Immune checkpoint inhibitor (ICI) have shown promising results against a variety of solid tumors across clinical trials. However, ICI monotherapy is often ineffective in patients with non-immunogenic tumors that exhibit high level of immunosuppression and low level of tumor infiltrating lymphocytes. To address these limitations, we have investigated a combination of ICIs [anti-PD-1 antibody (αPD-1), anti-PD-L1 antibody (αPD-L1), or anti-CTLA-4 antibody (αCTLA-4)] with several different immune stimulatory oncolytic adenoviruses (Ads) expressing different combinations of antitumor cytokines or immune modulatory factors [e.g., (1) interleukin (IL)-12 and granulocyte-macrophage colony-stimulating factor (GM-CSF; RdB/IL12/GMCSF), (2) IL-12 and short hairpin ribonucleic acid (shRNA) targeting vascular endothelial growth factor (RdB/IL12/shVEGF), (3) IL-12 and decorin (RdB/IL12/DCN), (4)…
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Taxonomy
TopicsCAR-T cell therapy research · Cancer Immunotherapy and Biomarkers · Immunotherapy and Immune Responses