New emerging targets in cancer immunotherapy: the role of neoantigens

Abstract

The success of cancer therapies with immune checkpoint inhibitors is transforming the treatment of patients with cancer and fostering cancer research. Therapies that target immune checkpoint inhibitors have shown unprecedented rates of durable long-lasting responses in patients with various cancer types, but only in a fraction of patients. Thus, novel approaches are needed to make immunotherapy more precise and also less toxic. The advances of next-generation sequencing technologies have allowed fast detection of somatic mutations in genes present in the exome of an individual tumour. Targeting neoantigens, the mutated peptides expressed only by tumour cells, may enable antitumour T-cell responses and tumour destruction without causing harm to healthy tissues. Currently, neoantigens can be identified in tumour clinical samples by using genomic-based computational tools. The two main treatment modalities targeting neoantigens that have been investigated in clinical trials are personalised vaccines and tumour infiltrating lymphocytes-based adoptive T-cell therapy. In this mini review, we discuss the promises and challenges for using neoantigens as emergent targets to personalise and guide cancer immunotherapy in a broader set of cancers.

Keywords: adoptive T cell; checkpoint inhibitors; immunotherapy; neoantigens; next generation sequencing; vaccines.

Figure 1

Two strategies targeting neoantigens as cancer immunotherapy. On the left: Neoantigen vaccination; from the tumour genome a computational pipeline is ran to identify neoantigens and after in vitro validation, a vaccine is designed and administrated to the patient. On the right: TIL-based adoptive T-cell therapy, T-cells removed from the patient are expanded and reinfused back to the patient (neoantigen-specific TIL based). APC, antigen presenting cells; MHC, major histocompatibility complex; NGS, next-generation sequencing; PD1, programmed cell death protein 1; PD-L1, programmed death-ligand 1; TIL, tumour infiltrating lymphocyte; TCR, T-cell receptor.