Yan Leyfman, Medical Oncologist, Co-Founder and Executive Director of MedNews Week, shared on X:
“Can targeting three antigens help overcome CAR T-cell resistance?
One of the biggest challenges after CD19 CAR T-cell therapy is disease relapse, often driven by loss or downregulation of CD19. A first-in-human Phase I trial evaluated a trispecific CAR T-cell engineered to simultaneously target CD19, CD20, and CD22, with the goal of reducing antigen escape.
Key findings:
- 16 patients with relapsed/refractory B-cell malignancies were treated
- Median vein-to-vein time: just 7 days
- No severe cytokine release syndrome or neurotoxicity was observed
- Overall response rate: 50%
- Among lymphoma patients, 83% achieved a complete response
- One-year overall survival: 61%, with durable remissions in several patients
Interestingly, CAR T-cell expansion did not correlate with dose or treatment response. Instead, higher T-cell exhaustion in the patient’s starting apheresis product was associated with progressive disease, highlighting the importance of T-cell fitness before manufacturing. While larger studies are needed, this early trial suggests that multi-antigen CAR T-cell therapies may help overcome one of the major mechanisms of relapse while maintaining a favorable safety profile. Congratulations to Dr DeLima and team on the amazing work!”
Title: Safety and clinical outcomes of a first-in-human trial of point-of-care manufactured trispecific CAR T cells targeting CD19, CD20, and CD22
Authors: Sumithira Vasu, Nathan Denlinger, No-Joon Song, Danielle Elsberry, Qiuhong Zhao, Lianbo Yu, Evandro D. Bezerra, Nicole Szuminski, Dina Schneider, Pradyot Dash, Louisa Wirthlin, Narendranath Epperla, Yazeed Sawalha, Jennifer A. Woyach, Shamama Nishat, Kerry A. Rogers, Seema A. Bhat, Hazem E. Ghoneim, Gregory K. Behbehani, Timothy J. Voorhees, Karilyn Larkin, Adam S. Kittai, Victoria Churchill, Elizabeth George, Margaret Lamb, Dean A. Lee, Wing Keung Chan, Ashley Krull, Rimas J. Orentas, Lynn O’Donnell, Zihai Li, Lapo Alinari, Marcos de Lima
Other articles about CAR T-cell therapy on OncoDaily.