Abstract
Abstract Novel anti-cancer immune therapeutic strategies, like various new antibody formats and/or tumor vaccines, show promising results in patients. However, due to the “immune-escape phenomenon” driven by tumor-secreted Transforming Growth Factor-beta (TGF-beta), the host immune system of cancer bearing patients frequently fails to control tumor re-growth. Real-Time Tumor Vaccincation (RealTVac) approach aims at avoiding this “immune-escape phenomenon” by intratumoral inhibition of active TGF-beta isotypes while simultanously and synergistically inducing an efficient immune response by a highly potent combination of immune stimulating factors. The synergistic effects of the proposed combination of a TGF-beta inhibitor with immunostimulating cytokines upon human immune cell activation are demonstrated in in-vitro experiments. Both, immune cell proliferation and tumor cell cytotoxicity were significantly enhanced. Initial experiments in a syngenic B16 melanoma xenograft model in immunocompetent mice indicate that Real-Time Tumor Vaccination of established subcutaneous B16 tumor xenografts reduced local tumor growth compared to untreated controls. To summarize, the goal of the local application of RealTVac is to allow the host immune system to scan in real-time all Tumor Associated Antigens (TAAs) being currently expressed by those tumor cells that are exposed to sufficient TGF-beta inhibition. The repetitive administration of the RealTVac approach is furthermore expected to provide a continuous update of the immune response, reflecting the changing pattern of currently expressed TAAs related to the dynamic intratumoral heterogeneity in malignant tumors. Thus, intratumoral immunization as applied for RealTVac may create a new paradigm for cancer therapy in the future. Citation Format: Piotr Jachimczak, Andreas Mitsch, Achim Aigner. RealTVac - a novel strategy to treat advanced, late-stage tumors with real-time tumor vaccination [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5585.
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