Engineered artificial antigen-presenting cells for tumor immunotherapy: Design strategies, clinical applications, and translational challenges

Immunotherapy has long played a pivotal role in cancer treatment, and antigen-presenting cell (APC)-based immunotherapy represents a promising strategy, though its full potential remains to be realized. This therapy stimulates T cell activation and proliferation through APCs, producing therapeutic effects. However, the use of natural APCs in immunotherapy faces several limitations, including inefficient T cell expansion, suboptimal targeting, and high treatment costs. Under such circumstances, artificial antigen-presenting cells (aAPCs) have garnered increasing interest. This review provides an overview of recent advancements in aAPCs research, systematically classifies aAPCs and critically evaluates their advantages and limitations. The underlying mechanisms of aAPCs, including activation and proliferation of T cells, strategies to overcome the immunosuppressive tumor microenvironment (TME), targeted antigen delivery and combination therapy, are discussed in detail. Their clinical applications are also debated. Existing challenges, including the absence of standardized protocols and regulatory frameworks, are highlighted. Furthermore, future directions in aAPCs technology are explored, including but not limited to the development of multifunctional aAPCs and the integration of artificial intelligence (AI) to assist in the design and optimization. Finally, to overcome these limitations, this review advocates for strengthened multidisciplinary collaboration and the adoption of emerging technologies.