A Personalized Cancer Nanovaccine that Enhances T‐Cell Responses and Efficacy Through Dual Interactions with Dendritic Cells and T Cells

Abstract Conventional approaches to developing therapeutic cancer vaccines that primarily activate tumor‐specific T cells via dendritic cells (DCs) often demonstrate limited efficacy due to the suboptimal activation of these T cells. To address this limitation, here a therapeutic cancer nanovaccine is developed that enhances T cell responses by interacting with both DCs and T cells. The nanovaccine is based on a cancer cell membrane nanoparticle (CCM‐MPLA) that utilizes monophosphoryl lipid A (MPLA) as an adjuvant. To allow direct interaction between the nanovaccine and tumor‐specific T cells, anti‐CD28 antibodies (aCD28) are conjugated onto CCM‐MPLA, resulting in CCM–MPLA–aCD28. This nanovaccine activates tumor‐specific CD8⁺ T cells in both the presence and absence of DCs. Compared with nanovaccines that interact with either DCs (CCM–MPLA) or T cells (CCM–aCD28), CCM–MPLA–aCD28 induces more potent responses of tumor‐specific CD8⁺ T cells and exhibits a higher antitumor efficacy in tumor‐bearing mice. No differences in T cell activation efficiency and therapeutic efficacy are observed between CCM–MPLA and CCM–aCD28. This approach may lead to the development of effective personalized therapeutic cancer vaccines prepared from autologous cancer cells.