Identification of neoantigen-reactive T lymphocytes in the peripheral blood of a patient with glioblastoma
Vid Leko, Gal Cafri, Rami Yossef, Biman C. Paria, Victoria Hill, Devikala Gurusamy, Zhili Zheng, Jared J. Gartner, Todd D. Prickett, Stephanie L. Goff, Paul F. Robbins, Yong‐Chen Lu, Steven A. Rosenberg
Abstract
The adoptive transfer of naturally occurring T cells that recognize cancer neoantigens has led to durable tumor regressions in select patients with cancer. However, it remains unknown whether such T cells can be isolated from and used to treat patients with glioblastoma, a cancer that is refractory to currently available therapies. To answer this question, we stimulated patient blood-derived memory T cells in vitro using peptides and minigenes that represented point mutations unique to patients’ tumors (ie, candidate neoantigens) and then tested their ability to specifically recognize these mutations. In a cohort of five patients with glioblastoma, we found that circulating CD4 + memory T cells from one patient recognized a cancer neoantigen harboring a mutation in the EED gene (EED H189N ) that was unique to that patient’s tumor. This finding suggests that neoantigen-reactive T cells could indeed be isolated from patients with glioblastoma, thereby providing a rationale for further efforts to develop neoantigen-directed adoptive T cell therapy for this disease.