Neoantigens in precision cancer immunotherapy: from identification to clinical applications

Abstract

Immunotherapies targeting cancer neoantigens are safe, effective, and precise. Neoantigens can be identified mainly by genomic techniques such as next-generation sequencing and high-throughput single-cell sequencing; proteomic techniques such as mass spectrometry; and bioinformatics tools based on high-throughput sequencing data, mass spectrometry data, and biological databases. Neoantigen-related therapies are widely used in clinical practice and include neoantigen vaccines, neoantigen-specific CD8+ and CD4+ T cells, and neoantigen-pulsed dendritic cells. In addition, neoantigens can be used as biomarkers to assess immunotherapy response, resistance, and prognosis. Therapies based on neoantigens are an important and promising branch of cancer immunotherapy. Unremitting efforts are needed to unravel the comprehensive role of neoantigens in anti-tumor immunity and to extend their clinical application. This review aimed to summarize the progress in neoantigen research and to discuss its opportunities and challenges in precision cancer immunotherapy.

Figure 1

T cell response induced by neoantigens. DC: Dendritic cell; NeoAg: Neoantigen; T: T cell.

Figure 2

The workflow of neoantigen identification. The whole workflow can be divided into five steps. The first step is sequencing of the cancer cells by WGS, WES or RNA-seq, etc. The following steps are variants calling, HLA typing and interactions prediction (interactions among HLA-neoantigen-TCR) based on the sequencing data. The last step is screening the interactions in vitro. ELISA: Enzyme-linked immunosorbent assay; GLIPH: Grouping of lymphocyte interactions by paratope hotspots; HLA: Human leukocyte antigen; INDELs: Short insertions and deletions; RNA-seq: RNA sequencing; SNPs: Single nucleotide polymorphisms; TCR: T cell receptor; WES: Whole exome sequencing; WGS: Whole genome sequencing.

Figure 3

Dynamic neoantigen tracking is used to evaluate the prognosis of cancer patients. This evaluation strategy can be more sensitive and reliable than imaging examination. Individualized gene panels are the key point to make this strategy sensitive and economical. ctDNA: Circulating tumor DNA.

Figure 4

Therapies based on neoantigens. CAR: Chimeric antigen receptor; DC: Dendritic cell.