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• W4207033496 abstract "Intratumoral immunotherapies are entering clinical use but concerns remain regarding their effects on non-injected tumors. Here, we studied the impact of local treatment with an adenovirus coding for TNFa and IL-2 on systemic antitumor response in animals receiving aPD-1 (anti-programmed cell death protein 1) therapy. Using bilateral murine melanoma models, we tested systemic tumor response to combined therapy with anti-PD-1 and an adenovirus coding for TNFa and IL-2 (virus). Virus was given intratumorally (to one of the two tumors only) and aPD-1 monoclonal antibody systemically. We evaluated both tumors' response to treatment, overall survival, metastasis development, and immunological mechanisms involved with response. Consistent tumor control was observed in both injected and non-injected tumors, including complete response in all treated animals receiving aPD-1+ virus therapy. Mechanistically, virus injections enabled potent effector lymphocyte response locally, with systemic effects in non-injected tumors facilitated by aPD-1 treatment. Moreover, adenovirus therapy demonstrated immunological memory formation. Virus therapy was effective in preventing metastasis development. Local treatment with TNFa and IL-2 coding adenovirus enhanced systemic response to aPD-1 therapy, by re-shaping the microenvironment of both injected and non-injected tumors. Therefore, our pre-clinical data support the rationale for a trial utilizing a combination of aPD-1 plus virus for the treatment of human cancer." @default.
• W4207033496 created "2022-01-26" @default.
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• W4207033496 date "2022-01-22" @default.
• W4207033496 modified "2023-10-14" @default.
• W4207033496 title "Local therapy with an engineered oncolytic adenovirus enables antitumor response in non-injected melanoma tumors in mice treated with aPD-1" @default.
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• W4207033496 doi "https://doi.org/10.1080/2162402x.2022.2028960" @default.
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