A PHASE 1, MULTICENTER, OPEN-LABEL STUDY OF CB-010, A NEXT-GENERATION CRISPR-EDITED ALLOGENEIC ANTI-CD19 CAR-T CELL THERAPY, IN PATIENTS WITH REFRACTORY SYSTEMIC LUPUS ERYTHEMATOSUS (GALLOP)

作者：Winn Chatham, S. Fiorenza, J. Weinmann-Menke, Olga Sánchez-Pernaute, R. Lafayette, A. Askanase, Michele Gerber, L. Alexander, Pingping Mao, E. Garner, George Kwong, Tristan W Fowler, Heinrich J Kufeldt, Brian Kerfs, Andrea Brown, C. Holland, K. Mcwilliams, G. Shah, A. Garrett, Mara Bryan, Linh Chu, Elaine Alambra, J. Skoble, Tom Kochy, T. Nesheiwat, Enrique Zudaire, Socorro Portella · 发表于：Journal of Rheumatology · 年份：2025 · DOI：10.3899/jrheum.2025-0390.pv119 · 被引用次数：1

PV119 / #87Poster Topic:AS15 - Lupus Nephritis-ClinicalAutologous CD19-directed CAR-T cell therapy led to deep depletion of aberrant B cells in lupus patients, leading to prolonged treatment-free remission in recent publications.[1] However, autologous CAR-T cell therapy is characterized by logistical challenges, including the need for leukapheresis, prolonged manufacturing and QC, and manufacturing failures. These may contribute to treatment delays and extended periods of treatment washout, compounding the risk for flares. Furthermore, the manufacturing time and logistics of autologous CAR-T cell therapies can limit their real-world feasibility and/or access for patients. CB-010 is an allogeneic, off-the-shelf anti-CD19 CAR-T cell therapy derived from healthy donor T cells. Patients receiving CB-010 do not require leukapheresis, thus eliminating the need for treatment washout preceding leukapheresis. CB-010 uses a next-generation genome-editing technology (chRDNA) to generate 3 genome edits: (i) knockout of theTRACgene to eliminate TCR expression to reduce the risk of graft-vs-host disease, (ii) site-specific insertion of a CD19-specific CAR into theTRAClocus, and (iii) knockout of the gene encoding PD-1, designed to increase cytotoxic activity against B cells. Importantly, PD-1 knockout in CB-010 has demonstrated a statistically significant benefit in efficacy inin vivopreclinical studies. CB-010 also features an FMC63 scFv and a 4-1BB costimulatory domain, a combination us...