First Human Trial of Off-the-Shelf CAR T-Cell Therapy Shows Promise

Last month at the virtual annual meeting of the American Association for Cancer Research (AACR), Chinese researchers announced results from the first human trial of an off-the-shelf CAR T-cell therapy, GC027, to treat T-cell acute lymphocytic leukemia (T-ALL). The study was a collaborative effort between Shanghai-based Gracell Biotechnologies and several hospitals in the cities of Kunming and Chongqing.

While other CAR T-cell treatments, such as Novartis’ tisagenlecleucel and Gilead’s axicabtagene ciloleucel, are manufactured from T-cells harvested from patients, GC027 is developed from the T-cells of healthy donors.

“The quality of T cells obtained from healthy donors may be higher than the quality of T cells found in [cancer] patients,” especially those who have received chemotherapy or radiation, said Yvonne Chen, PhD, of the University of California, Los Angeles (UCLA). “This could, in turn, result in more robust therapeutic efficacy.”

The trial involved a small single-arm study of 5 patients, aged 19 to 38, with T-ALL and up to 80% malignant bone marrow cells. All 5 patients had previously relapsed after standard treatment. Each received a single infusion of GC027. Four months after the infusion, 1 patient showed no enduring benefit, but the remaining 4 showed robust CAR T-cell expansion and achieved persistent minimal residual disease−negative complete remission.

All 5 patients experienced similar serious adverse events to CAR T-cell therapies already in use, including cytokine release syndrome. “The clinical benefit is limited by [that] high toxicity,” said AACR Program Committee Chair Antoni Ribas, MD, also of UCLA.

Previous CAR T-cell treatments required a 3-to-4-week manufacturing process, and some patients’ health would decline too quickly to receive the completed therapy. An off-the-shelf version could be available much sooner.

Though tisagenlecleucel and axicabtagene ciloleucel are intended to treat other leukemias and lymphomas, there are no CAR T-cell options currently available for patients with T-ALL, which represents about a quarter of ALL cases in adults. The current treatment prognosis for T-ALL is grim: 40 to 50% of patients who respond to chemotherapy eventually relapse and then fail to respond to next-line treatments; fewer than 25% survive after relapse. An off-the-shelf CAR T-cell therapy could provide a critical new option for these patients.

Sources: STAT, April 28, 2020; Wang X, Li S, Gao L, et al. Clinical safety and efficacy study of TruUCAR™ GC027: The first-in-human, universal CAR-T therapy for adult relapsed/refractory T-cell acute lymphoblastic leukemia (r/r T-ALL). Presented at the AACR Virtual Annual Meeting, April 28, 2020.