Biomaterial‐Based In Situ Cancer Vaccines

Abstract

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.

Advances in Cancer Vaccine Research

“…(C) Design criteria and antitumor efficacy of the cancer vaccines. Panel C reproduced with permission from ref . Copyright 2023 Wiley-VCH.…”

“…Cancer vaccines have many advantages when used in cancer immunotherapy: (a) Cancer vaccines have tumor antigen specificity, which induces a strong immune response to antigens specifically expressed by tumor cells; (b) the safety of cancer vaccines is high; and (c) cancer vaccines can induce immune memory and trigger long-term immunity, helping to control tumor recurrence . The historical efficacy of cancer vaccines has been limited, but novel designs for new antigens and other targets offer hope for the future (Figure C) . Several conditions are required for the preparation of cancer vaccines: (1) The correct TAA is essential to stimulate effective T cells.…”

“…28 The historical efficacy of cancer vaccines has been limited, but novel designs for new antigens and other targets offer hope for the future (Figure 1C). 29 Several conditions are required for the preparation of cancer vaccines: (1) The correct TAA is essential to stimulate effective T cells. (2) Achieving sufficient antigen concentration in the dc and activating the DCs.…”

Dendritic Cell-Based In Situ Nanovaccine for Reprogramming Lipid Metabolism to Boost Tumor Immunotherapy

“…In situ vaccines could widely activate the local immune response at the tumor site by inducing tumor cell death which could release TAAs. 14,15 More importantly, these antigens are employed directly, avoiding the identification of TAAs in different patients, which provides the possibility of widespread use of cancer vaccines. 16 Currently, most of the cancer vaccines are devoted to enhancing adaptive T-cell responses by stimulating APCs with antigen carriers, adjuvants, and engineered dendritic cells (DCs).…”

“…Accordingly, it underscores the urgency of developing a facile and powerful therapeutic vaccine. In situ vaccines could widely activate the local immune response at the tumor site by inducing tumor cell death which could release TAAs. , More importantly, these antigens are employed directly, avoiding the identification of TAAs in different patients, which provides the possibility of widespread use of cancer vaccines …”