T cell stimulation and expansion by SunTag-based clustering of anti-CD3/CD28 scFv.

Kunhong Zhong, Zhiyong Liu, Hongjian Li, Shasha Zhao, Yuelong Wang, Wenhao Guo, Xi Zheng, Hui Yang, Gang Guo, Liangxue Zhou, Jianguo Xu, Aiping Tong

Aging 2020 Jun 10

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Therapeutic ex vivo T cell expansion is limited by low rates and poor functionality, especially for T cells from aged cancer patients. Here, we describe a novel method for T cell stimulation and expansion using a system named SunTag-based clustering of anti-CD3/CD28 scFv (SBCS). In this method, SunTag was used to recruit up to 13 copies of anti-CD3/CD28 scFv for T cell activation. Compared with the traditional method using immobilized CD3/CD28 antibodies, the SBCS system produced approximately 1.5-fold greater expansion of T cells from healthy donors, and more than 2-fold greater expansion of T cells from aged cancer patients after stimulation. The efficiency of expansion depended mainly on the concentration of the clustered polymers of anti-CD3 scFv rather than anti-CD28 scFv. We also demonstrated that the SBCS-expanded T cells could be used to prepare functional chimeric antigen receptor modified T cells for antitumor therapy.

Citation

Kunhong Zhong, Zhiyong Liu, Hongjian Li, Shasha Zhao, Yuelong Wang, Wenhao Guo, Xi Zheng, Hui Yang, Gang Guo, Liangxue Zhou, Jianguo Xu, Aiping Tong. T cell stimulation and expansion by SunTag-based clustering of anti-CD3/CD28 scFv. Aging. 2020 Jun 10;12(11):11061-11070