Biomaterial‐Based In Situ Cancer Vaccines

Cancer immunotherapies have reshaped the paradigm for cancer treatment over the past decade. Among them, therapeutic cancer vaccines that aim to modulate antigen-presenting cells and subsequent T cell priming processes are among the first FDA-approved cancer immunotherapies. However, despite showing benign safety profiles and the capability to generate antigen-specific humoral and cellular responses, cancer vaccines have been limited by the modest therapeutic efficacy, especially for immunologically cold solid tumors. One key challenge lies in the identification of tumor-specific antigens, which involves a costly and lengthy process of tumor cell isolation, DNA/RNA extraction, sequencing, mutation analysis, epitope prediction, peptide synthesis, and antigen screening. To address these issues, in situ cancer vaccines have been actively pursued to generate endogenous antigens directly from tumors and utilize the generated tumor antigens to elicit potent cytotoxic T lymphocyte (CTL) response. Biomaterials-based in situ cancer vaccines, in particular, have achieved significant progress by taking advantage of biomaterials that can synergize antigens and adjuvants, troubleshoot delivery issues, home, and manipulate immune cells in situ. This review will provide an overview of biomaterials-based in situ cancer vaccines, either living or artificial materials, under development or in the clinic, and discuss the design criteria for in situ cancer vaccines.