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Int. J. Mol. Sci. 2017, 18(12), 2773; doi:10.3390/ijms18122773

Lym-1 Chimeric Antigen Receptor T Cells Exhibit Potent Anti-Tumor Effects against B-Cell Lymphoma

1
Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
2
Department of Physiology and Neuroscience, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
*
Authors to whom correspondence should be addressed.
Received: 28 November 2017 / Revised: 14 December 2017 / Accepted: 15 December 2017 / Published: 20 December 2017
(This article belongs to the Special Issue Chimeric Antigen Receptor (CAR) T Cell Therapy)
View Full-Text   |   Download PDF [3978 KB, uploaded 20 December 2017]   |  

Abstract

T cells expressing chimeric antigen receptors (CARs) recognizing CD19 epitopes have produced remarkable anti-tumor effects in patients with B-cell malignancies. However, cancer cells lacking recognized epitopes can emerge, leading to relapse and death. Thus, CAR T cells targeting different epitopes on different antigens could improve immunotherapy. The Lym-1 antibody targets a conformational epitope of Human Leukocyte Antigen-antigen D Related (HLA-DR) on the surface of human B-cell lymphomas. Lym-1 CAR T cells were thus generated for evaluation of cytotoxic activity towards lymphoma cells in vitro and in vivo. Human T cells from healthy donors were transduced to express a Lym-1 CAR, and assessed for epitope-driven function in culture and towards Raji xenografts in NOD-scidIL2Rgammanull (NSG) mice. Lym-1 CAR T cells exhibited epitope-driven activation and lytic function against human B-cell lymphoma cell lines in culture and mediated complete regression of Raji/Luciferase-Green fluorescent protein (Raji/Luc-GFP) in NSG mice with similar or better reactivity than CD19 CAR T cells. Lym-1 CAR transduction of T cells is a promising immunotherapy for patients with Lym-1 epitope positive B-cell malignancies. View Full-Text
Keywords: cancer immunotherapy; lymphoma; CAR T cells; Lym-1 cancer immunotherapy; lymphoma; CAR T cells; Lym-1
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Zheng, L.; Hu, P.; Wolfe, B.; Gonsalves, C.; Ren, L.; Khawli, L.A.; Kaslow, H.R.; Epstein, A.L. Lym-1 Chimeric Antigen Receptor T Cells Exhibit Potent Anti-Tumor Effects against B-Cell Lymphoma. Int. J. Mol. Sci. 2017, 18, 2773.

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