Clonal cancer neoantigen

Clonal cancer neoantigens are proteins derived from somatic mutations that occur early in a tumor's development, resulting in their expression across all malignant cells in a patient (McGranahan et al., 2016, Science). These truncal mutations are ideal targets for immunotherapy because they represent a uniform vulnerability, reducing the likelihood of therapeutic resistance caused by intratumor heterogeneity (Luksza et al., 2017, Nature). These antigens are processed and presented on the cell surface by Major Histocompatibility Complex (MHC) molecules, where they can be recognized by CD8+ and CD4+ T cells (Schumacher & Schreiber, 2015, Science). Current clinical approaches to target these neoantigens include personalized vaccines, such as mRNA-4157 and RO7198457, as well as adoptive cell therapies like tumor-infiltrating lymphocytes (TILs) (Ott et al., 2017, Nature; Sahin et al., 2017, Nature). By specifically directing the immune system toward clonal targets, these therapies aim to achieve complete and durable responses in various solid tumors.

Other names

Truncal neoantigenTrunk mutation-derived neoantigenClonal tumor-specific antigenClonal TSAShared tumor-specific antigen

Induction of a targeted T-cell mediated immune response against mutations present in the trunk of the tumor's phylogenetic tree, ensuring that all tumor cells are susceptible to T-cell killing (McGranahan et al., 2016, Science; Schumacher & Schreiber, 2015, Science).