Efficacy of B7-H3-Redirected BiTE and CAR-T Immunotherapies Against Extranodal Nasal Natural Killer/T Cell Lymphoma |
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| Institution: | 1. Department of Otolaryngology, Head and Neck Surgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan province, PR China;2. State Key Laboratory of Biotherapy, West China Medical School, Sichuan University, Chengdu, Sichuan province, PR China;3. Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan province, PR China;4. Department of Laboratory Medicine, West China Medical School, Sichuan University, Chengdu, Sichuan province, PR China |
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| Abstract: | Extranodal nasal natural killer (NK)/T cell lymphoma (ENKTCL) is a rare but highly aggressive subtype of non-Hodgkin lymphoma (NHL). Nevertheless, despite extensive research, the estimated 5-year overall survival of affected patients remains low. Therefore, new treatment strategies are needed urgently. Recent advances in immunotherapy have the potential to broaden the applications of chimeric antigen receptor-modified T (CAR-T) cells and the bispecific T-cell engaging (BiTE) antibody. Here, we screened a panel of biomarkers including the B7-H3, CD70, TIM-3, VISTA, ICAM-1, and PD-1 in NKTCL cell lines. As a result, we found for the first time that B7-H3 was highly and homogeneously expressed in these cells. Consequently, we constructed a novel anti-B7-H3/CD3 BiTE antibody and B7-H3-redirected CAR-T cells, and evaluated their efficacy against NKTCL cel lines both in vitro and in vivo. Notably, we found that both anti-B7-H3/CD3 BiTE and B7-H3-redirected CAR-T cells effectively targeted and killed NKTCL cells in vitro, and suppressed the growth of NKTCL tumors in NSG mouse models. Thus, B7-H3 might be a promising therapeutic target for treating patients with NKTCL tumors. |
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