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Efficacy of B7-H3-Redirected BiTE and CAR-T Immunotherapies Against Extranodal Nasal Natural Killer/T Cell Lymphoma

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 urgent...

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Detalles Bibliográficos
Autores principales: Zheng, Meijun, Yu, Lingyu, Hu, Juanjuan, Zhang, Zongliang, Wang, Haiyang, Lu, Dan, Tang, Xin, Huang, Jianhan, Zhong, Kunhong, Wang, Zeng, Li, Yisong, Guo, Gang, Liu, Shixi, Tong, Aiping, Yang, Hui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Neoplasia Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7160598/
https://www.ncbi.nlm.nih.gov/pubmed/32298986
http://dx.doi.org/10.1016/j.tranon.2020.100770
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author Zheng, Meijun
Yu, Lingyu
Hu, Juanjuan
Zhang, Zongliang
Wang, Haiyang
Lu, Dan
Tang, Xin
Huang, Jianhan
Zhong, Kunhong
Wang, Zeng
Li, Yisong
Guo, Gang
Liu, Shixi
Tong, Aiping
Yang, Hui
author_facet Zheng, Meijun
Yu, Lingyu
Hu, Juanjuan
Zhang, Zongliang
Wang, Haiyang
Lu, Dan
Tang, Xin
Huang, Jianhan
Zhong, Kunhong
Wang, Zeng
Li, Yisong
Guo, Gang
Liu, Shixi
Tong, Aiping
Yang, Hui
author_sort Zheng, Meijun
collection PubMed
description 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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spelling pubmed-71605982020-04-22 Efficacy of B7-H3-Redirected BiTE and CAR-T Immunotherapies Against Extranodal Nasal Natural Killer/T Cell Lymphoma Zheng, Meijun Yu, Lingyu Hu, Juanjuan Zhang, Zongliang Wang, Haiyang Lu, Dan Tang, Xin Huang, Jianhan Zhong, Kunhong Wang, Zeng Li, Yisong Guo, Gang Liu, Shixi Tong, Aiping Yang, Hui Transl Oncol Original article 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. Neoplasia Press 2020-04-13 /pmc/articles/PMC7160598/ /pubmed/32298986 http://dx.doi.org/10.1016/j.tranon.2020.100770 Text en © 2020 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original article
Zheng, Meijun
Yu, Lingyu
Hu, Juanjuan
Zhang, Zongliang
Wang, Haiyang
Lu, Dan
Tang, Xin
Huang, Jianhan
Zhong, Kunhong
Wang, Zeng
Li, Yisong
Guo, Gang
Liu, Shixi
Tong, Aiping
Yang, Hui
Efficacy of B7-H3-Redirected BiTE and CAR-T Immunotherapies Against Extranodal Nasal Natural Killer/T Cell Lymphoma
title Efficacy of B7-H3-Redirected BiTE and CAR-T Immunotherapies Against Extranodal Nasal Natural Killer/T Cell Lymphoma
title_full Efficacy of B7-H3-Redirected BiTE and CAR-T Immunotherapies Against Extranodal Nasal Natural Killer/T Cell Lymphoma
title_fullStr Efficacy of B7-H3-Redirected BiTE and CAR-T Immunotherapies Against Extranodal Nasal Natural Killer/T Cell Lymphoma
title_full_unstemmed Efficacy of B7-H3-Redirected BiTE and CAR-T Immunotherapies Against Extranodal Nasal Natural Killer/T Cell Lymphoma
title_short Efficacy of B7-H3-Redirected BiTE and CAR-T Immunotherapies Against Extranodal Nasal Natural Killer/T Cell Lymphoma
title_sort efficacy of b7-h3-redirected bite and car-t immunotherapies against extranodal nasal natural killer/t cell lymphoma
topic Original article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7160598/
https://www.ncbi.nlm.nih.gov/pubmed/32298986
http://dx.doi.org/10.1016/j.tranon.2020.100770
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