Abstract 3526: A novel strategy to treat advanced, late-stage tumors with real-time tumor vaccination “Online Vaccine”

Abstract Malignant cells acquired immunoevasive properties by numerous mechanisms allowing them to form locally invasive and metastatic tumors resistant to current therapeutic strategies. TGF-beta overexpression in tumor cells correlates with malignant progression by induction of “immune-escape phenomenon” in cancer bearing patients. Real-Time approach to generate a Tumor Vaccine in vivo (“Online Vaccine”) aims at avoiding this, immune-escape phenomenon“ by intratumoral inhibition of TGF-beta function while simultaneously and synergistically inducing an efficient anti-tumor immune response. The synergistic effects of the proposed combination of a TGF-beta inhibitor with immunostimulating cytokines IL-2 and GM-CSF (RealTVac®) upon human immune cell activation has been demonstrated in vitro and in vivo. This, four-dimensional (4D)-approach to treat advanced, late-stage, malignant tumor by use of repetitive spacio (intratumoral) - temporal (real-time) combination therapy 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 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, Paul Jachimczak. A novel strategy to treat advanced, late-stage tumors with real-time tumor vaccination “Online Vaccine” [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3526.