Journal for immunotherapy of cancer
CD83 CAR T provides an alternative strategy to CD19-targeting in B cell malignancies
By Betts BC, Savid-Frontera C, McSain S and 13 others.
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.