Tumor membrane vesicle (TMV)-based cancer vaccine induces dendritic cell maturation and downstream T cell activation

Breast cancer remains the most commonly diagnosed cancers among American women, with over 250,000 new cases expected per year. Breast cancer can be subdivided into different categories depending on the expression of receptors, most commonly into ER+, PR+, HER2+, and TNBC. Clinically, small molecule inhibitors of the hormone receptors and antibodies for HER2 have been developed to target these receptors and inhibit tumor signaling or eliminate these cells via phagocytosis and ADCC. Despite this, tumor cells that develop resistance to therapy remain a significant unmet need as they tend to be more aggressive and metastasize. We developed a novel immunotherapy approach that addresses the high degree of inter-patient and intra-tumor heterogeneity by making tumor membrane vesicle (TMV) vaccines out of individual tumor samples and modifying them with GPI-linked molecules like IL-12 and B7-1 to induce an antitumor immune response. In the present study, we investigated whether GPI-GM-CSF and GPI-IL-12 on TMVs from HER2+ murine breast cancer can target and activate antigen presenting cells. Here, we show that TMVs containing with GPI-GM-CSF and GPI-IL-12 can be phagocytosed by both macrophages and dendritic cells, induce upregulation of MHC-I, MHC-II and CD86, and inflammatory cytokine production in vitro. Further, when the DCs activated with our TMV vaccine were co-cultured with syngeneic T cells, they induced the upregulation of T cell activation markers. In summary, our results indicate that TMVs containing GPI-IL-12 and GPI-GM-CSF can enhance uptake and maturation of APCs and induce a strong T cell response downstream making it a potential therapeutic approach for HER2+ breast cancer.