Exploring immunomodulatory tumor-derived vaccines targeting triple negative breast cancer cells

Breast cancer remains a major public health concern and is the leading cause of cancer-related deaths among women. Triple-negative breast cancer (TNBC) is the subtype with the poorest prognosis, and due to its phenotypic characteristics, no effective treatment is currently available for most diagnosed patients. This underscores the urgent need for novel therapeutic strategies. In this project, we explore antitumor vaccines generated from genetically modified TNBC cells expressing the immunomodulatory ligands TNFSF 4-1BBL and OX-40L. TNFSF ligands have the ability to costimulate T cells, enhancing their activation and proliferation. Previous studies from our group demonstrated that such vaccine combinations can increase T-cell proliferation, boost interferon-gamma production, inhibit regulatory T cells, and enhance T cell-mediated antitumor cytotoxicity, leading to a long term antitumor immunity and preventing tumor recurrence in cured and rechallenged animal models. Here, we generated antitumor vaccines derived from human TNBC cells, which were obtained after neoadjuvant chemotherapy from a patient sample provided by the CAISM-UNICAMP biobank. These cells were genetically engineered to express OX-40L and 4-1BBL, and the resulting tumor cell-based vaccines were evaluated in vitro for their antitumor potential. We observed that the vaccines enhanced immune responses in T lymphocytes from both autologous and allogeneic TNBC vaccines. Experimental assays confirmed that these tumor-derived vaccines induced elevated production of immunomodulatory cytokines and improved the antitumor T cell-mediated cytotoxicity. Our findings support the potential of this strategy as a promising immunotherapy approach for TNBC. Ethical approval CAAE: 08897219.9.0000.5404 Supported by CNPq 308403/2022-3, and FAPESP 2023/12245-0