Citations 2
Targeting chronic lymphocytic leukemia with B‐cell activating factor receptor CAR T cells
Qie, Yaqing, To, Tommy, Li, Shuhua, Rivera-Valentín, Rocío K. , Dronca, Roxana , Kharfan‐Dabaja, Mohamed A. , Gadd, Martha E. , Shao, Qing , Yassine, Farah, Shao, Qing , Liu, Andy , Yassine, Farah , Murthy, Hemant S. , Qin, Hong , Luo, Yan
MedComm | September 2, 2024 | Volume: 5 | Issue: 9 | Pages: No page available
AbstractThe challenge of disease relapsed/refractory (R/R) remains a therapeutic hurdle in chimeric antigen receptor (CAR) T‐cell therapy, especially for hematological diseases, with chronic lymphocytic leukemia (CLL) being particularly resistant to CD19 CAR T cells. Currently, there is no approved CAR T‐cell therapy for CLL patients. In this study, we aimed to address this unmet medical need by choosing the B‐cell activating factor receptor (BAFF‐R) as a promising target for CAR design against CLL. BAFF‐R is essential for B‐cell survival and is consistently expressed on CLL tumors. Our research discovered that BAFF‐R CAR T‐cell therapy exerted the cytotoxic effects on both CLL cell lines and primary B cells derived from CLL patients. In addition, the CAR T cells exhibited cytotoxicity against CD19‐knockout CLL cells that are resistant to CD19 CAR T therapy. Furthermore, we were able to generate BAFF‐R CAR T cells from small blood samples collected from CLL patients and then demonstrated the cytotoxic effects of these patient‐derived CAR T cells against autologous tumor cells. Given these promising results, BAFF‐R CAR T‐cell therapy has the potential to meet the long‐standing need for an effective treatment on CLL patients.
Cutting Edge: Cbl-b: One of the Key Molecules Tuning CD28- and CTLA-4-Mediated T Cell Costimulation
Gál, István, Vermes, Csaba , Alegre, Maria-Luisa, Shao, Qing , Adarichev, Vyacheslava, Xu, Xuemei , Koreny, Tamás, Mikecz, Katalin , Finnegan, Alison, Glant, Tibor T., Zhang, Jian , Li, Dongdong , Alegre, Maria‐Luisa , Chong, Anita S. , Chen, Lieping , Adarichev, Vyacheslav A.
The Journal of Immunology | April 20, 2014 | Volume: 173 | Issue: 12 | Pages: 7135-7139
Abstract Cbl-b negatively regulates CD28-dependent T cell activation. In this report, we tested the hypothesis that CD28 and CTLA-4 have opposite roles in tuning T cell activation threshold by controlling the levels of Cbl-b protein expression. We demonstrate that CD28 costimulation potentiates TCR-induced Cbl-b degradation, whereas CTLA-4-B7 interaction is required for Cbl-b re-expression. In support of this finding, Cbl-b expression in CTLA-4 knockout (KO) T cells is significantly reduced, and treating CTLA-4KO mice with human CTLA-4Ig to block CD28-B7 interaction restores Cbl-b expression on T cells. Furthermore, CD28 and CTLA-4 costimulatory effects are compromised in Cbl-bKO T cells. These observations indicate that CD28 and CTLA-4 tightly regulate Cbl-b expression which is critical for establishing the threshold for T cell activation.