Shared neoantigens for cancer immunotherapy.

Exploration of neoantigens holds the potential to be productive in immuno-oncotherapy. Among tumor-specific antigens, neoantigens result from genetic instability that gives rise to non-synonymous somatic mutations, highly specific to tumor cells. In addition to point mutations, gene rearrangements, indels leading to frameshifts, chromosomal translocations or inversions that may lead to fusion proteins, alternative mRNA splicing, and integration of genetic material of oncogenic viruses into the host genome provide consistent sources of neoantigens that are absent in healthy tissues. Out of these alterations, 2%-3% may generate T cell neoepitopes, possibly detectable by TCRs. Neoantigens are absent in healthy tissues and are thus at low risk of triggering autoimmunity. In addition, the host lymphocytes have not been rendered tolerant toward them and it is possible to induce immune responses against them. Here, we overview the two categories of neoantigens, i.e., private and shared, and their use in immuno-oncotherapy in selected pre-clinical and clinical studies. The vast majority of commonly occurring tumor-specific mutations are cancer causing and are permanently expressed by all malignant tumor cells, preventing the latter from escaping vaccine-induced anti-neoantigen immunity. The use of public neoantigens combined with efficient vaccine platforms can provide non-personalized "off-the-shelf" therapeutic vaccine candidates for broad-spectrum immunotherapy purposes.