Myeloid Cell‐Triggered In Situ Cell Engineering for Robust Vaccine‐Based Cancer Treatment

Abstract Following the success of the dendritic cell (DC) vaccine, the cell‐based tumor vaccine shows its promise as a vaccination strategy. Except for DC cells, targeting other immune cells, especially myeloid cells, is expected to address currently unmet clinical needs (e.g., tumor types, safety issues such as cytokine storms, and therapeutic benefits). Here, it is shown that an in situ injected macroporous myeloid cell adoptive scaffold (MAS) not only actively delivers antigens (Ags) that are triggered by scaffold‐infiltrating cell surface thiol groups but also releases granulocyte–macrophage colony‐stimulating factor and other adjuvant combos. Consequently, this promotes cell differentiation, activation, and migration from the produced monocyte and DC vaccines (MASVax) to stimulate antitumor T‐cell immunity. Neoantigen‐based MASVax combined with immune checkpoint blockade induces rejection of established tumors and long‐term immune protection. The combined depletion of immunosuppressive myeloid cells further enhances the efficacy of MASVax, indicating the potential of myeloid cell‐based therapies for immune enhancement and normalization treatment of cancer.