S42 molecular remissions in patients with treatment-resistant T-ALL. Systemic ablation of T- and NK-cells was limited due to the repopulation with CD7-negative lymphocyte subsets mirroring the mechanism observed post CD5 CAR T-cell infusion. Similar outcomes have been observed in clinical trials outside the US using autologous and allogeneic CD7 CAR T-cells where fratricide was mitigated by CD7 genome editing or PEBL-mediated disruption of surface expression.6,7 Collectively these results illustrate feasibility, safety, and preliminary efficacy of CAR T-cells targeting pan-T cell antigens CD5 and CD7 for the therapy of treatment-refractory or relapsed T-ALL and LBL. References 1. Maksim Mamonkin, Rayne H. Rouce, Haruko Tashiro, Malcolm K. Brenner. A T-cell–directed chimeric antigen receptor for the selective treatment of T-cell malignancies. Blood. 2015; 126(8): 983–992. 2. Gomes-Silva D, Srinivasan M, Sharma S, Lee CM, Wagner DL, Davis TH, Rouce RH, Bao G, Brenner MK, Mamonkin M. CD7-edited T cells expressing a CD7specific CAR for the therapy of T-cell malignancies. Blood. 2017;130(3):285-296. 3. Yi Tian Png, Natasha Vinanica, Takahiro Kamiya, Noriko Shimasaki, Elaine Coustan-Smith, Dario Campana. Blockade of CD7 expression in T cells for effective chimeric antigen receptor targeting of T-cell malignancies. Blood Adv. 2017; 1(25): 2348–2360. 4. Matthew L Cooper et al. An “off-the-shelf” fratricideresistant CAR-T for the treatment of T cell hematologic malignancies. Leukemia. 2018; 32: 1970–1983 5. Norihiro Watanabe et al. Feasibility and preclinical efficacy of CD7-unedited CD7 CAR T cells for T cell malignancies. Mol Ther. 2023;31(1):24-34. 6. Yongxian Hu et al. Genetically modified CD7-targeting allogeneic CAR-T cell therapy with enhanced efficacy for relapsed/refractory CD7-positive hematological malignancies: a phase I clinical study. Cell Res. 2022; 32(11):995-1007. 7. Jing Pan et al. Donor-Derived CD7 Chimeric Antigen Receptor T Cells for T-Cell Acute Lymphoblastic Leukemia: First-in-Human, Phase I Trial. Journal of Clinical Oncology. 2021; 39(30): 3340-3351.
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