Prospective Identification of Neoantigen-Specific T-Cell Receptors Using an Optimized Model System


Adoptive cell transfer (ACT) is a type of immunotherapy in which immune cells that react to cancer are infused into a patient. T cells can be engineered to specifically bind neoantigens – cancer cell proteins that carry patient-specific cancer mutations – prior to transfer. Current methods for identifying neoantigen-specific T-cell receptors that can be exploited for therapeutic purposes are inefficient. Dr. Michelle Krogsgaard of New York University School of Medicine and her team are addressing this gap by developing mice with a comprehensive and diverse repertoire of humanized T cells that can be screened to identify T-cell receptors (TCRs) that react in a personalized way to an individual patient’s cancer and their neoantigens.  TCRs identified using this platform could be engineered into the patient’s own T cells and then used for adoptive cell transfer. The results of this project could broaden the pool of cancer patients who benefit from personalized immunotherapy treatments.