The ability to specifically engage tumor-reactive T cells for therapeutic benefit is the ultimate goal of cancer immunotherapy. Whereas currently approved immunotherapies leverage and modulate existing endogenous T cells in an antigen non-specific manner, cancer vaccines and neoantigen therapeutics promise the ability to selectively amplify T cells specific for targeted antigens. Advances in the identification of tumor-specific antigens coupled with a greater understanding of T cell biology and immunization platforms have culminated in recent trials where signs of clinical efficacy have been observed, particularly in randomized adjuvant clinical settings. In this review, we discuss the identification of tumor-specific antigens for cancer therapy, the benefits of including antigens recognized by CD4+ T cells, clinical data investigating novel immunization platforms, and emerging clinical settings where promotion of tumor-specific immunity may be optimal.
Mirabile-Brightman et al. (2026) studied this question.