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Targeting B7-H3 via chimeric antigen receptor T cells and bispecific killer cell engagers augments antitumor response of cytotoxic lymphocytes
Liu, J.; Yang, S.; Cao, B.; Zhou , G.; Zhang, F.; Wang, Y.; Wang, R.; Zhu, L.; Meng, Y.; Hu, C.; Liang, H.; Lin, X.; Zhu, K.; Chen, G.; Luo, K.Q.; Di, L.; Zhao, Q.
2021-01-29
Source PublicationJournal of Hematology & Oncology
ISSN557-3265
Pages1-18
AbstractPurpose: B7-H3, an immune-checkpoint molecule, a transmembrane protein, is overexpressed in non-small cell lung cancer (NSCLC), making it an attractive therapeutic target. Here, we aimed to systematically evaluate the value of B7-H3 as a target in NSCLC via T cells expressing B7-H3-specific chimeric antigen receptors (CARs) and bispecific killer cell engager (BiKE)-redirected natural killer (NK) cells. Experimental design: We generated B7-H3 CAR and B7-H3/CD16 BiKE derived from an anti-B7-H3 antibody omburtamab that has been shown to preferentially bind tumor tissues and has been safely used in humans in early-phase clinical trials. Antitumor efficacy and induced-immune response of CAR and BiKE were evaluated in vitro and in vivo. The effects of B7-H3 on aerobic glycolysis in NSCLC cells were further investigated. Results: B7-H3 CAR-T cells effectively inhibited NSCLC tumorigenesis in NSCLC models. B7-H3 redirection promoted highly specific T-cell infiltration into tumors. Additionally, natural killer (NK) cell activity could be specially triggered by B7-H3/CD16 BiKE through direct CD16 signaling, resulting in significant increase in NK cell activation and target cell death. BiKE improved antitumor efficacy mediated by NK cells in vitro and in vivo, regardless of the cell surface target antigen density on tumor tissues. Furthermore, we found that anti-B7-H3 blockade might alter tumor glucose metabolism via the reactive oxygen species-mediated pathway. Conclusions: Together, our results suggest that B7-H3 may serve as a target for NSCLC therapy and support the further development of two therapeutic agents in the preclinical and clinical studies.
KeywordB7-H3 chimeric antigen receptor bispecific antibody non-small cell lung
URLView the original
Language英語English
The Source to ArticlePB_Publication
PUB ID54543
Document TypeJournal article
CollectionDEPARTMENT OF BIOMEDICAL SCIENCES
Corresponding AuthorZhao, Q.
Recommended Citation
GB/T 7714
Liu, J.,Yang, S.,Cao, B.,et al. Targeting B7-H3 via chimeric antigen receptor T cells and bispecific killer cell engagers augments antitumor response of cytotoxic lymphocytes[J]. Journal of Hematology & Oncology,2021:1-18.
APA Liu, J.,Yang, S.,Cao, B.,Zhou , G.,Zhang, F.,Wang, Y.,Wang, R.,Zhu, L.,Meng, Y.,Hu, C.,Liang, H.,Lin, X.,Zhu, K.,Chen, G.,Luo, K.Q.,Di, L.,&Zhao, Q..(2021).Targeting B7-H3 via chimeric antigen receptor T cells and bispecific killer cell engagers augments antitumor response of cytotoxic lymphocytes.Journal of Hematology & Oncology,1-18.
MLA Liu, J.,et al."Targeting B7-H3 via chimeric antigen receptor T cells and bispecific killer cell engagers augments antitumor response of cytotoxic lymphocytes".Journal of Hematology & Oncology (2021):1-18.
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