Details

Autor(en) / Beteiligte

• 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

Titel

CD318 is a target of chimeric antigen receptor T cells for the treatment of colorectal cancer

Ist Teil von

• Clinical and experimental medicine, 2023-10, Vol.23 (6), p.2409-2419

Ort / Verlag

Cham: Springer International Publishing

Erscheinungsjahr

2023

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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.