Targeting Driver Oncogenes and Other Public Neoantigens Using T Cell Receptor–Based Cellular Therapy

T cell reactivity to tumor-specific neoantigens can drive endogenous and therapeutically induced antitumor immunity. However, most are unique each patient (private) targeting them requires personalized therapy. A smaller subset of includes epitopes that span recurrent mutation hotspots, translocations, or gene fusions in oncogenic drivers tumor suppressors, as well arise from viral proteins. Such antigens likely be shared across patients (public), uniformly expressed within a tumor, required for cancer survival fitness. Although limited number these public naturally immunogenic, recent studies affirm their clinical utility. In this review, we highlight efforts target mutant KRAS, p53, derived viruses using cells engineered with off-the-shelf receptors. We also discuss the challenges strategies achieving more effective therapies, particularly context solid tumors. Expected final online publication date Annual Review Cancer Biology, Volume 7 is April 2023. Please see http://www.annualreviews.org/page/journal/pubdates revised estimates.