Personalized cancer neoantigen vaccines come of age

Abstract

Cancer vaccines have encountered their ideal personalized partner along with evidence for great breakthroughs in the identification and synthesis of neoantigens. Individual cancer neoantigen vaccines are capable of eliciting robust T-cell responses and have been demonstrated to achieve striking clinical efficacy due to their high immunogenicity and central thymic tolerance escape of neoantigens. Two recent phase I clinical trials have provided support for the hypothesis and have heralded a nascent era of personalized vaccines in the field of immunotherapy. This review aims to address the identification of neoepitopes and describes advances made in personalized vaccines. In addition, this review discusses the challenges related to the exploitation of vaccine therapy, and provides potential thoughts for the improvement of vaccine design and applications.

Keywords: Neoantigen; T-cell response; immunotherapy; vaccine.

Figure 1

Three common approaches to neoantigen identification. Approach A: tumour-specific mutations are identified by WES, confirmed by RNA sequencing, and then ranked by predicted high-affinity binding to autologous HLA types; finally, neopeptides are synthesized based on prioritized mutated alleles, which is followed by T-cell reactivity analysis ex vivo to confirm their immunogenicity. Approach B: based on tumour-specific mutations identified by WES, TMG constructs are synthesized as templates for the generation of IVT RNA, which is followed by T-cell reactivity analysis ex vivo to confirm their immunogenicity. Approach C: mutation identification is based on research from databases and the literature. The next steps can be the same as those for either of the two methods described above. APCs: antigen-presenting cells; HLA: human leukocyte antigen; PBMCs: peripheral blood mononuclear cells; TMG: tandem minigene; WES: whole-exome sequencing.