Work

CD83 CAR T provides an alternative strategy to CD19-targeting in B cell malignancies

Year: 2026

Type: article

Abstract: Background Chimeric antigen receptor T cells (CAR T) targeting CD19 can cure patients with aggressive B cell malignancies. Relapse due to CD19 loss and infections from B cell aplasia remain major causes of death after CD19 CAR T. We demonstrate that CD83 is a clinically relevant target for CAR T therapy in B cell malignancies, overcoming limitations of CD19 CAR T.Methods We evaluate CD83 expression among B cell acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), diffuse large B cell lymphoma (DLBCL), and circulating healthy B cells, compared with CD19, CD20, and CD22. We test the activity of CD19 and CD83 CAR T against Raji and Nalm6 target cells using in vitro and in vivo preclinical models. Functional and immunophenotypic aspects of CD19 and CD83 CAR T are investigated to compare potency. Further, we evaluate CD19 and CD83 expression on B cell ALL after prior CD19-directed therapy, revealing a propensity for CD19 antigen loss. To simulate CD19 antigen loss, we test CD19 and CD83 CAR T against CD19 knock-out Nalm6 cells.Results CD83 is expressed on B-cell ALL, MCL, and DLBCL, with negligible expression on circulating B cells and CLL. B cell ALL expresses CD83 at diagnosis and on relapse following CD19-directed therapy, when CD19 is decreased. CD83 CAR T kills B cell leukemia/lymphoma cell lines in vitro, providing efficacy after CD19 antigen loss. We show CD83 CAR T is effective as monotherapy in mice. Exploratory experiments suggest CD83 CAR T may offer enhanced efficacy when administered sequentially after CD19 CAR T.Conclusions Our preclinical evidence justifies further translational investigation of CD83 CAR T in B cell leukemia and lymphoma. The benefits of CD83 CAR T include a low risk for B cell aplasia and efficacy after exposure to CD19 CAR T.

Source: Journal for ImmunoTherapy of Cancer

DOI: 10.1136/jitc-2025-013670