Cancer vaccines as promising immuno-therapeutics: platforms and current progress

Abstract

Research on tumor immunotherapy has made tremendous progress in the past decades, with numerous studies entering the clinical evaluation. The cancer vaccine is considered a promising therapeutic strategy in the immunotherapy of solid tumors. Cancer vaccine stimulates anti-tumor immunity with tumor antigens, which could be delivered in the form of whole cells, peptides, nucleic acids, etc. Ideal cancer vaccines could overcome the immune suppression in tumors and induce both humoral immunity and cellular immunity. In this review, we introduced the working mechanism of cancer vaccines and summarized four platforms for cancer vaccine development. We also highlighted the clinical research progress of the cancer vaccines, especially focusing on their clinical application and therapeutic efficacy, which might hopefully facilitate the future design of the cancer vaccine.

Keywords: Cancer vaccine; Clinical application; Immunotherapy; Tumor antigens; Tumor resistance.

Fig. 1

Tumor-immune cycle induced by cancer vaccines. The immune response that effectively kills tumor cells involves steps that allow repetition and expansion called the tumor-immune cycle. After the administration of the tumor vaccine, DCs uptake and process tumor antigens, then present them to MHC II or MHC I (through cross-presentation). Antigen-loaded DCs migrate to lymph nodes to recruit and activate immune cells. Follicular DCs promote the generation of memory B cells and plasma cells. Activated B cells promote tumor apoptosis through ADCC. Activated T cells proliferate and differentiate into memory T cells and effector T cells. Effector T cells travel to TME, killing tumor cells directly or inducing tumor cell apoptosis. Immunogenic dead tumor cells can release TAAs and danger signaling molecules to increase the depth and breadth of the response in subsequent cycles

Fig. 2

Resistance of cancer vaccines. a Tumor external resistance. Immunosuppressive cells (such as CAFs, MDSCs, Tregs, and M2 macrophages) and immunosuppressive cytokines can inhibit the activation of effector T cells and DC-mediated T cells directly or indirectly in TME. b Tumor intrinsic resistance. The intrinsic resistance of tumor contains six aspects: the mutations in signaling pathways supporting tumor-immune control; the loss of tumor antigen expression; the changes in antigen processing pathways; the loss of HLA expression; epigenetic changes; increased expression of immunosuppressive ligands c Immune selection: from immunosurveillance to tumor escape

Fig. 3

Mechanism of cancer vaccines. Compared to peptide-based vaccines, nucleic acid-based vaccines need more processing steps after entering the body before being presented to T cells by DCs. However, DNA and RNA vaccines are better suited to deliver MHC I presentation antigens than peptide vaccines. Tumor antigens are processed by DCs and transported to the cell surface of MHC I and MHC II molecules. Interaction between MHC–peptide complex–T cell receptor (TCR) and cognate receptor-ligand pairs activate T cells. Activated CD4⁺ T cells induce B cells to differentiate into plasma cells and memory B cells. Activated T cells differentiated into CD8⁺ memory T cells and CD8⁺ effector T cells. Eventually, effector T cells, B cells, antibodies, and some cytokines kill tumor cells directly or indirectly