DNA Engineered Lymphocyte-Based Homologous Targeting Artificial Antigen-Presenting Cells for Personalized Cancer Immunotherapy

Artificial antigen-presenting cells (aAPCs) con-structed by integrating T cell activation ligands on biocompatiblematerials hold great potential in tumor immunotherapy. However,it remains challenging to develop aAPCs, which could mimic thecharacteristics of natural APCs, thereby realizing antigen-specificTcells activationin vivo. Here, we report thefirst effort to constructnatural lymphocyte-based homologous targeting aAPCs (LC-aAPCs) with lipid-DNA-mediated noninvasive live cell surfaceengineering. Through a predesigned bottom-up self-assembly path,we achieved natural-APC-mimicking distribution of T cellactivation ligands on LC-aAPCs, which would enable theoptimized T cell activation. Moreover, the lipid-DNA-mediatedself-assembly occurring on lipid bilayers would not affect thefunctions of homing receptors expressed on lymphocyte. Therefore, such LC-aAPCs could actively migrate to peripheral lymphaticorgans and then effectively activate antigen-specific T cells. Combined with an immune checkpoint inhibitor, such LC-aAPCs couldeffectively inhibit the growth of different tumor models. Thus, our work provides a new design of aAPCs forin vivoapplications intumor immunotherapy, and the lipid-DNA-mediated noninvasive live cell surface engineering would be a powerful tool for designingcell-based therapeutics.