| Autor: |
Li, Ming, Li, Shanglin, Zhao, Ruocong, Lv, Jiang, Zheng, Diwei, Qin, Le, Li, Siyu, Wu, Qiting, Long, Youguo, Tang, Zhaoyang, Tang, Yan-Lai, Yang, Lihua, Yao, Yao, Luo, Xuequn, Li, Peng |
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| Zdroj: |
Clinical & Experimental Medicine; Oct2023, Vol. 23 Issue 6, p2409-2419, 11p |
| Abstrakt: |
Colorectal cancer (CRC) currently has a poor prognosis with a 6.9-year median survival time; to relieve this malignant cancer, we proposed to establish CRC xenografts that can be used to evaluate the cytotoxicity of adoptive chimeric antigen receptor (CAR)-T cells and accelerate the clinical translation of CAR-T cells for use against CRC. We first verified that CD318 had a higher expression level in primary human CRC tissues than in normal tissues based on hundreds of clinical samples. Then, we redirected CAR-T cells containing anti-CD318 single-chain variable fragment (anti-CD318 scFv), CD3ζ, CD28, and Toll-like receptor 2 (TLR2) domains. Next, we evaluated the function of these CAR-T cells in vitro in terms of surface phenotype changes, cytotoxicity and cytokine secretion when they encountered CD318+ CRC cells. Finally, we established two different xenograft mouse models to assess in vivo antitumor activity. The results showed that CAR318 T cells were significantly activated and exhibited strong cytotoxicity and cytokine-secreting abilities against CRC cells in vitro. Furthermore, CAR318 T cells induced CRC regression in different xenograft mouse models and suppressed tumors compared with CAR19 T cells. In summary, our work demonstrates that CAR318 T cells possess strong antitumor capabilities and represent a promising therapeutic approach for CRC. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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