Vaccines (Oct 2020)

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

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

DOI
https://doi.org/10.3390/vaccines8040631
Journal volume & issue
Vol. 8, no. 4
p. 631

Abstract

Read online

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.

Keywords