Antitumor efficacy and safety of unedited autologous CD5.CAR T cells in relapsed/refractory mature T-cell lymphomas.

Autor:	Hill LC; Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, TX.; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX., Rouce RH; Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, TX.; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX.; Department of Pediatrics, Baylor College of Medicine, Houston, TX., Wu MJ; Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, TX.; Biostatistics Shared Resource, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX., Wang T; Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, TX.; Biostatistics Shared Resource, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX., Ma R; Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, TX., Zhang H; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX., Mehta B; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX., Lapteva N; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX., Mei Z; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX., Smith TS; Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, TX., Yang L; Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, TX., Srinivasan M; Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, TX., Burkhardt PM; Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, TX., Ramos CA; Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, TX.; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX., Lulla P; Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, TX.; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX., Arredondo M; Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, TX., Grilley B; Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, TX., Heslop HE; Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, TX.; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX.; Department of Pediatrics, Baylor College of Medicine, Houston, TX., Brenner MK; Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, TX.; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX.; Department of Pediatrics, Baylor College of Medicine, Houston, TX., Mamonkin M; Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, TX.; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX.
Jazyk:	angličtina
Zdroj:	Blood [Blood] 2024 Mar 28; Vol. 143 (13), pp. 1231-1241.
DOI:	10.1182/blood.2023022204
Abstrakt:	Abstract: Despite newer targeted therapies, patients with primary refractory or relapsed (r/r) T-cell lymphoma have a poor prognosis. The development of chimeric antigen receptor (CAR) T-cell platforms to treat T-cell malignancies often requires additional gene modifications to overcome fratricide because of shared T-cell antigens on normal and malignant T cells. We developed a CD5-directed CAR that produces minimal fratricide by downmodulating CD5 protein levels in transduced T cells while retaining strong cytotoxicity against CD5+ malignant cells. In our first-in-human phase 1 study (NCT0308190), second-generation autologous CD5.CAR T cells were manufactured from patients with r/r T-cell malignancies. Here, we report safety and efficacy data from a cohort of patients with mature T-cell lymphoma (TCL). Among the 17 patients with TCL enrolled, CD5 CAR T cells were successfully manufactured for 13 out of 14 attempted lines (93%) and administered to 9 (69%) patients. The overall response rate (complete remission or partial response) was 44%, with complete responses observed in 2 patients. The most common grade 3 or higher adverse events were cytopenias. No grade 3 or higher cytokine release syndrome or neurologic events occurred. Two patients died during the immediate toxicity evaluation period due to rapidly progressive disease. These results demonstrated that CD5.CAR T cells are safe and can induce clinical responses in patients with r/r CD5-expressing TCLs without eliminating endogenous T cells or increasing infectious complications. More patients and longer follow-up are needed for validation. This trial was registered at www.clinicaltrials.gov as #NCT0308190. (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)
Databáze:	MEDLINE
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