Patient-specific tumor neoantigen-specific T cells (NeoT cells)

Patient-specific tumor neoantigen-specific T cells are a personalized therapeutic modality within adoptive cell therapy (ACT) that leverages the immune system's ability to recognize unique somatic mutations (Schumacher & Schreiber, 2015, Science). These cells are typically derived from a patient's own tumor-infiltrating lymphocytes (TILs) or peripheral blood and are selected or engineered to express T-cell receptors (TCRs) that specifically bind to neoantigens—mutated proteins found exclusively in tumor cells (Rosenberg & Restifo, 2015, Science). Upon recognition of these neoantigens presented by Major Histocompatibility Complex (MHC) molecules, the T cells execute a targeted cytotoxic attack, releasing perforins and granzymes to induce tumor cell apoptosis (Ott et al., 2017, Nature). This high specificity theoretically reduces the risk of on-target, off-tumor toxicity compared to therapies targeting shared self-antigens. Clinical efficacy is often monitored through biomarkers such as tumor mutational burden (TMB) and TCR clonality (Yarchoan et al., 2017, NEJM). However, therapeutic success can be limited by the immunosuppressive tumor microenvironment and the potential for T-cell exhaustion or poor persistence in vivo.

Other names

Neoantigen-reactive T cellsNRTsMutation-specific T cellsNeoantigen-primed T cellsNeoantigen-specific tumor-infiltrating lymphocytes

Recognition of MHC-presented neoantigens via TCR, leading to T-cell activation, cytokine release, and direct tumor cell lysis.