Progress in Neoantigen Targeted Cancer Immunotherapies

Abstract

Immunotherapies that harness the immune system to kill cancer cells have showed significant therapeutic efficacy in many human malignancies. A growing number of studies have highlighted the relevance of neoantigens in recognizing cancer cells by intrinsic T cells. Cancer neoantigens are a direct consequence of somatic mutations presenting on the surface of individual cancer cells. Neoantigens are fully cancer-specific and exempt from central tolerance. In addition, neoantigens are important targets for checkpoint blockade therapy. Recently, technological innovations have made neoantigen discovery possible in a variety of malignancies, thus providing an impetus to develop novel immunotherapies that selectively enhance T cell reactivity for the destruction of cancer cells while leaving normal tissues unharmed. In this review, we aim to introduce the methods of the identification of neoantigens, the mutational patterns of human cancers, related clinical trials, neoantigen burden and sensitivity to immune checkpoint blockade. Moreover, we focus on relevant challenges of targeting neoantigens for cancer treatment.

Keywords: cancer immunotherapy; checkpoint blockade; clinical trial; neoantigens; targeted cancer.

FIGURE 1

A framework for the identification and prioritization of neoantigens from computational analysis for an individual cancer sample.

FIGURE 2

Profiling the humoral immune response and the process of protein microarray to capture autoantibodies against antigens.

FIGURE 3

Schematic diagram illustrates the steps involved in tumor neoantigen processing and presentation on MHC class I molecules.