FCCC LOGO Faculty Publications
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 (Basel). 2020 Oct 31;8(4)
PMID: 33142718    PMCID: PMC7711665    URL: https://www.ncbi.nlm.nih.gov/pubmed/33142718
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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.
Wang, Jie Urbanska, Katarzyna Sharma, Prannda Nejati, Reza Shaw, Lauren Orcid: 0000-0002-4104-2261 Lim, Megan S Schuster, Stephen J Jr, Daniel J Powell R01 CA168900/CA/NCI NIH HHS/United States R01 CA168900/NH/NIH HHS/United States R01 EB026892/EB/NIBIB NIH HHS/United States R01 EB026892/NH/NIH HHS/United States T32 GM008076/GM/NIGMS NIH HHS/United States T32 GM008076/NH/NIH HHS/United States Journal Article Switzerland Vaccines (Basel). 2020 Oct 31;8(4):E631. doi: 10.3390/vaccines8040631.