Therapeutic Vaccines Targeting Neoantigens to Induce T-Cell Immunity against Cancers

Abstract

Cancer immunotherapy has achieved multiple clinical benefits and has become an indispensable component of cancer treatment. Targeting tumor-specific antigens, also known as neoantigens, plays a crucial role in cancer immunotherapy. T cells of adaptive immunity that recognize neoantigens, but do not induce unwanted off-target effects, have demonstrated high efficacy and low side effects in cancer immunotherapy. Tumor neoantigens derived from accumulated genetic instability can be characterized using emerging technologies, such as high-throughput sequencing, bioinformatics, predictive algorithms, mass-spectrometry analyses, and immunogenicity validation. Neoepitopes with a higher affinity for major histocompatibility complexes can be identified and further applied to the field of cancer vaccines. Therapeutic vaccines composed of tumor lysates or cells and DNA, mRNA, or peptides of neoantigens have revoked adaptive immunity to kill cancer cells in clinical trials. Broad clinical applicability of these therapeutic cancer vaccines has emerged. In this review, we discuss recent progress in neoantigen identification and applications for cancer vaccines and the results of ongoing trials.

Neoantigens: promising targets for cancer therapy

“…Neoantigen-loaded DC vaccines can expand the antigenic breadth and clonal diversity of anti-tumor immunity. 9,112,[356][357][358][359][360][361] Several clinical trials are investigating the efficacy and safety of personalized neoantigen DC vaccines in solid tumors, such as melanoma, bladder cancer, colorectal cancer, esophageal cancer, breast cancer, ovarian cancer, pancreatic cancer, hepatocellular carcinoma, lung cancer, and gastric cancer (Table 4).…”

Scoring model based on the signature of non-m6A-related neoantigen-coding lncRNAs assists in immune microenvironment analysis and TCR-neoantigen pair selection in gliomas

“…Due to its specificity in tumor immunity, these are considered promising targets for immunotherapy [ 63 ]. Recently, the neoantigen vaccine’s ability to induce T-cell-mediated immunity has been widely discussed [ 9 , 63 , 64 ]. Some circumstantial evidence advocates for the reinvigoration of exhausted T cells in tumor patients.…”

Development of therapeutic vaccines for the treatment of diseases

“…These TAAs are self-molecules abnormally expressed by tumor cells or the "non-self " antigens of oncogenic viruses. They include cancer testis antigens (e.g., MAGE-A1, MAGE-A3, and NY-ESO-1), which are restricted to only immune privileged germline cells and have no or low expression in normal adult somatic cells [171,172]; differentiation antigens (e.g., tyrosinase, gp100, MART-1, PSA and PAP), which are normally not expressed in adult tissue [173]; overexpressed antigens (e.g., RAGE-1, hTERT, HER2, mesothelin, and MUC-1), which are aberrantly overexpressed in tumor cells compared to normal cells [174]; and oncoviral products (e.g., E6/E7 proteins from HPV) [175]. However, several hurdles are associated with therapeutic vaccination focused on TAAs, resulting in unsuccessful and ineffective antitumor immune responses.…”