A Novel Approach for the Treatment of T Cell Malignancies: Targeting T Cell Receptor Vβ Families

Wang, Jie; Urbanska, Katarzyna; Sharma, Prannda; Nejati, Reza; Shaw, Lauren; Lim, Megan S.; Schuster, Stephen J.; Jr., Daniel J. Powell

doi:10.3390/vaccines8040631

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A Novel Approach for the Treatment of T Cell Malignancies: Targeting T Cell Receptor Vβ Families

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Division of Hematologic Malignancies and Cellular Therapies, Duke Cancer Institute, Durham, NC 27710, USA

Bristol-Meyers Squibb, 345 Park Ave, New York, NY 10154, USA

Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA

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Department of Pathology, Fox Chase Cancer Center, 333 Cottman Ave, Philadelphia, PA 19111, USA

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Division of Hematology/Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA

Author to whom correspondence should be addressed.

Vaccines 2020, 8(4), 631; https://doi.org/10.3390/vaccines8040631

Received: 24 August 2020 / Revised: 12 October 2020 / Accepted: 26 October 2020 / Published: 31 October 2020

(This article belongs to the Special Issue Cancer Vaccines and Immunotherapy for Tumor Prevention and Treatment)

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Abstract

Peripheral T cell lymphomas (PTCLs) are generally chemotherapy resistant and have a poor prognosis. The lack of targeted immunotherapeutic approaches for T cell malignancies results in part from potential risks associated with targeting broadly expressed T cell markers, namely T cell depletion and clinically significant immune compromise. The knowledge that the T cell receptor (TCR) β chain in human α/β TCRs are grouped into Vβ families that can each be targeted by a monoclonal antibody can therefore be exploited for therapeutic purposes. Here, we develop a flexible approach for targeting TCR Vβ families by engineering T cells to express a chimeric CD64 protein that acts as a high affinity immune receptor (IR). We found that CD64 IR-modified T cells can be redirected with precision to T cell targets expressing selected Vβ families by combining CD64 IR-modified T cells with a monoclonal antibody directed toward a specific TCR Vβ family in vitro and in vivo. These findings provide proof of concept that TCR Vβ-family-specific T cell lysis can be achieved using this novel combination cell–antibody platform and illuminates a path toward high precision targeting of T cell malignancies without substantial immune compromise. View Full-Text

Keywords: T cell lymphoma; T cell receptor; antibodies; immunotherapy; CD64; immune receptor

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MDPI and ACS Style

Wang, J.; Urbanska, K.; Sharma, P.; Nejati, R.; Shaw, L.; Lim, M.S.; Schuster, S.J.; Jr., D.J.P. A Novel Approach for the Treatment of T Cell Malignancies: Targeting T Cell Receptor Vβ Families. Vaccines 2020, 8, 631. https://doi.org/10.3390/vaccines8040631

AMA Style

Wang J, Urbanska K, Sharma P, Nejati R, Shaw L, Lim MS, Schuster SJ, Jr. DJP. A Novel Approach for the Treatment of T Cell Malignancies: Targeting T Cell Receptor Vβ Families. Vaccines. 2020; 8(4):631. https://doi.org/10.3390/vaccines8040631

Chicago/Turabian Style

Wang, Jie, Katarzyna Urbanska, Prannda Sharma, Reza Nejati, Lauren Shaw, Megan S. Lim, Stephen J. Schuster, and Daniel J. Powell Jr. 2020. "A Novel Approach for the Treatment of T Cell Malignancies: Targeting T Cell Receptor Vβ Families" Vaccines 8, no. 4: 631. https://doi.org/10.3390/vaccines8040631

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A Novel Approach for the Treatment of T Cell Malignancies: Targeting T Cell Receptor Vβ Families

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