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Research Paper|Volume 12, Issue 11|pp 11061—11070

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

Kunhong Zhong1, Zhiyong Liu2, Hongjian Li1, Shasha Zhao1, Yuelong Wang2, Wenhao Guo1, Xi Zheng3, Hui Yang4, Gang Guo1, Liangxue Zhou2, Jianguo Xu2, Aiping Tong1
  • 1State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan Province, China
  • 2Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, China
  • 3Lung Cancer Center, West China Hospital, Sichuan University, Chengdu, China
  • 4Department of Otolaryngology, Head and Neck Surgery, West China Hospital, Sichuan University, Chengdu, China
* Equal contribution
Received: February 12, 2020Accepted: April 28, 2020Published: June 10, 2020
https://doi.org/10.18632/aging.103318

Copyright © 2020 Zhong et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

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.