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Conventional dendritic cell (DC) therapies have delivered mixed clinical results. We have recently developed new platforms of gene-modified DCs designed to activate the immune system against cancer. These platforms use DC progenitors (DCPs) engineered to express cytokine payloads and/or novel chimeric receptors. These modifications enable DCs to capture extracellular vesicles (EVs) released from the patient’s own tumor and present EV-associated tumor antigens to the immune system, without requiring prior knowledge or ex vivo manipulation of tumor antigens. Our engineered DCPs represent a new class of cell therapy products for personalized therapeutic applications, which combine well with other anti-cancer treatments such as chemo-immunotherapy and CAR-T cells. We are committed to clinically testing our DC-based strategies and delivering them to patients with cancer.
Our lab has contributed to elucidating the pro-angiogenic and pro-tumoral functions of macrophages in mouse cancer models. We have also characterized VEGFA-independent mechanisms of tumor angiogenesis and demonstrated the therapeutic potential of inhibiting angiopoietin signaling in de novo models of metastatic cancer. Currently, we use mouse models of lung cancer, melanoma, and glioblastoma, together with cell-engineering strategies, to disrupt pro-tumoral networks orchestrated by macrophages and blood vessels, while strengthening anti-tumoral networks driven by dendritic cells and T cells. Through these approaches, we aim to reprogram the immunosuppressive tumor microenvironment into one that enhances the efficacy of anticancer therapies and supports the activation of anti-tumor immunity.