CD83 CAR T provides an alternative strategy to CD19-targeting in B cell malignancies
- 1Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA
- 2Blood and Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, Florida, USA
- 3University of Minnesota Twin Cities, Minneapolis, Minnesota, USA
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.
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BibTeX
@article{betts2026cd83,
title = {{CD83 CAR T provides an alternative strategy to CD19-targeting in B cell malignancies}},
author = {Brian Christopher Betts and Constanza Savid-Frontera and Shannon McSain and Kelly Walton and Eliese Maybee and Nolan Beatty and Payal Goala and Duna Massillon and Isaac M Spiegel and Shernan G Holtan and Frederick L Locke and Anne Eaton and Michael A Linden and Meredith L Stone and Renier J Brentjens and Marco L Davila},
journal = {Journal for Immunotherapy of Cancer},
year = {2026},
month = oct,
doi = {10.1136/jitc-2025-013670},
url = {https://doi.org/10.1136/jitc-2025-013670},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - CD83 CAR T provides an alternative strategy to CD19-targeting in B cell malignancies
AU - Brian Christopher Betts
AU - Constanza Savid-Frontera
AU - Shannon McSain
AU - Kelly Walton
AU - Eliese Maybee
AU - Nolan Beatty
AU - Payal Goala
AU - Duna Massillon
AU - Isaac M Spiegel
AU - Shernan G Holtan
AU - Frederick L Locke
AU - Anne Eaton
AU - Michael A Linden
AU - Meredith L Stone
AU - Renier J Brentjens
AU - Marco L Davila
PY - 2026
DA - 2026/10/26
JO - Journal for Immunotherapy of Cancer
DO - 10.1136/jitc-2025-013670
UR - https://doi.org/10.1136/jitc-2025-013670
AB - 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.
SN - 2051-1426
ER -