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
Published in
Blood cancer discovery. Jul 14, 2026. Epub Jul 14, 2026.
Abstract
Disease recurrence is the main cause of treatment failure after CD19-directed CAR T cells, often due to CD19 antigen loss, stability and/or coverage. To overcome single-antigen escape, we evaluated a trispecific CAR targeting CD19, CD20, and CD22 with OX40 co-stimulatory domain. Preclinical studies demonstrated potent, antigen-specific cytotoxicity in in vitro and in vivo lymphoma models. We then conducted a first-in-human phase I trial in patients with relapsed/refractory B-cell malignancies. Sixteen patients received infusions at a median vein-to-vein time of 7 days, at doses of 0.5-2×10⁶ cells/kg. No severe cytokine release syndrome nor neurotoxicity occurred. Overall response rate was 50%, including complete responses in 83% of lymphoma patients. One-year overall survival rate was 61%, with durable remissions observed in lymphoma. CAR T expansion did not correlate with dose or response. T-cell exhaustion in apheresis cells correlated with progressive disease. Trispecific CAR T cells are safe and potentially active in lymphoma.
PMID:
42446920
Bibliographic data and abstract were imported from PubMed on 14 Jul 2026.
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