Neoantigen-directed therapeutics in the clinic: where are we?

Abstract

In the past decade, immune checkpoint inhibitors (ICIs) and chimeric antigen receptor (CAR) T cell therapy have brought immunotherapy to the forefront of cancer treatment; however, only subsets of patients benefit from current approaches. Neoantigen-driven therapeutics specifically redirect the immune system of the patient to enable or reinduce its ability to recognize and eliminate cancer cells. The tumor specificity of this strategy spares healthy and normal cells from being attacked. Consistent with this concept, initial clinical trials have demonstrated the feasibility, safety, and immunogenicity of neoantigen-directed personalized vaccines. We review neoantigen-driven therapy strategies as well as their promise and clinical successes to date.

Keywords: T cell; T cell receptor; cell therapy; neoantigen; personalized; vaccine.

Figure 1.. Comparison of cancer vaccination versus transgenic TCR T cell therapy: manufacture and mechanism of action.

Abbreviations: DC, dendritic cell; IV, intravenous; MHC, major histocompatibility complex; TCR, T cell receptor.

Figure 2.. Different approaches for neoantigen-directed T cell therapy.

Abbreviations: HLA, human lymphocyte antigen; neoTCR, neoantigen-specific TCR; PBMC, peripheral blood mononuclear leukocyte; TCR, T cell receptor; TIL, tumor-infiltrating lymphocyte.

Figure 3.

Window of opportunity platform/basket clinical trial design setup suitable for personalized therapeutics to test multiple therapies at the same time, thus enabling informed decision concerning the optimal combination therapy.