Oh et al. report the safety and efficacy of fratricide-resistant anti-CD7 PEBL-CAR T cells in 17 patients with relapsed or refractory T-ALL. Despite high leukemic burden, the CAR T cells expanded robustly in vivo. 16 out of 17 patients attained MRD-negative remission within one month of infusion, 11 remained relapse-free, and 1 showed long-term remission even after 55 months without transplant. The treatment was safe and manageable. T cells regenerated after lymphodepletion lacked CD7 expression, were polyclonal, and responded to SARS-CoV-2 vaccination, and CD7+ immune cells reappeared with the disappearance of CAR T cells.
Contributed by Shishir Pant
ABSTRACT: T cell acute lymphoblastic leukemia (T-ALL) is difficult to treat when it relapses after therapy or is chemoresistant; the prognosis of patients with relapsed or refractory T-ALL is generally poor. We report a case series of 17 such patients who received autologous chimeric antigen receptor (CAR) T cells expressing an anti-CD7 CAR and an anti-CD7 protein expression blocker (PEBL), which prevented CAR T cell fratricide. Despite high leukemic burden and low CAR T cell dosing, 16 of the 17 patients attained minimal residual disease-negative complete remission within 1 month. The remaining patient had CD7(-) T-ALL cells before infusion, which persisted after infusion. Toxicities were mild: cytokine release syndrome grade 1 in ten patients and grade 2 in three patients; immune effector cell-associated neurotoxicity syndrome grade 1 in two patients. Eleven patients remained relapse-free (median follow-up, 15 months), including all nine patients who received an allotransplant. The first patient is in remission 55 months after infusion without further chemotherapy or transplantation; circulating CAR T cells were detectable for 2 years. T cells regenerating after lymphodepletion lacked CD7 expression, were polyclonal and responded to SARS-CoV-2 vaccination; CD7(+) immune cells reemerged concomitantly with CAR T cell disappearance. In conclusion, autologous anti-CD7 PEBL-CAR T cells have powerful antileukemic activity and are potentially an effective option for the treatment of T-ALL.
Author Info: (1) Viva-University Children's Cancer Center, Khoo Teck Puat-National University Children's Medical Institute, National University Hospital, National University Health System, Sing
Author Info: (1) Viva-University Children's Cancer Center, Khoo Teck Puat-National University Children's Medical Institute, National University Hospital, National University Health System, Singapore, Singapore. Department of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. (2) Department of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. (3) Department of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. (4) National University Cancer Institute, National University Hospital, National University Health System, Singapore, Singapore. (5) National University Cancer Institute, National University Hospital, National University Health System, Singapore, Singapore. (6) Viva-University Children's Cancer Center, Khoo Teck Puat-National University Children's Medical Institute, National University Hospital, National University Health System, Singapore, Singapore. Department of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. (7) Viva-University Children's Cancer Center, Khoo Teck Puat-National University Children's Medical Institute, National University Hospital, National University Health System, Singapore, Singapore. Department of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. (8) National University Cancer Institute, National University Hospital, National University Health System, Singapore, Singapore. (9) Division of Infectious Diseases, Department of Medicine, National University Health System, Singapore, Singapore. (10) Emerging Infectious Diseases Programme, Duke-NUS Medical School, Singapore, Singapore. (11) Emerging Infectious Diseases Programme, Duke-NUS Medical School, Singapore, Singapore. (12) Emerging Infectious Diseases Programme, Duke-NUS Medical School, Singapore, Singapore. (13) Department of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. (14) Department of Pediatric Hematology/Oncology and Cell and Gene Therapy, IRCCS Ospedale Pediatrico Bambino Ges, Rome, Italy. (15) Department of Pediatric Hematology/Oncology and Cell and Gene Therapy, IRCCS Ospedale Pediatrico Bambino Ges, Rome, Italy. (16) Department of Pediatric Hematology/Oncology and Cell and Gene Therapy, IRCCS Ospedale Pediatrico Bambino Ges, Rome, Italy. franco.locatelli@opbg.net. Department of Life Sciences and Public Health, Catholic University of the Sacred Heart, Rome, Italy. franco.locatelli@opbg.net. (17) Viva-University Children's Cancer Center, Khoo Teck Puat-National University Children's Medical Institute, National University Hospital, National University Health System, Singapore, Singapore. paeyej@nus.edu.sg. Department of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. paeyej@nus.edu.sg. National University Cancer Institute, National University Hospital, National University Health System, Singapore, Singapore. paeyej@nus.edu.sg. Cancer Science Institute, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. paeyej@nus.edu.sg. (18) Department of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. National University Cancer Institute, National University Hospital, National University Health System, Singapore, Singapore. Cancer Science Institute, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
