Research Papers:
Retargeted human avidin-CAR T cells for adoptive immunotherapy of EGFRvIII expressing gliomas and their evaluation via optical imaging
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Abstract
Kaiyu Liu1,*, Xujie Liu2,*, Zhiping Peng2, Haojie Sun3,4, Mingzhi Zhang3,4, Jianning Zhang5, Shuang Liu5, Limin Hao6, Guoqiu Lu6, Kangcheng Zheng6, Xikui Gong6, Di Wu6, Fan Wang7,8 and Li Shen3,4
1 Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing, People’s Republic of China
2 Department of Radiological Medicine, Chongqing Medical University, Chongqing, People’s Republic of China
3 Department of Cell Biology, Peking University Health Science Center, Beijing, People’s Republic of China
4 Peking University Stem Cell Research Center, Beijing, People’s Republic of China
5 Department of Neurosurgery, The Chinese PLA Navy General Hospital, Beijing, People’s Republic of China
6 Beijing Cellonis Biotechnologies Co., Ltd, Zhongguancun Bio-Medicine Park, Beijing, People’s Republic of China
7 Medical Isotopes Research Center, Peking University, Beijing, People’s Republic of China
8 Department of Radiation Medicine, School of Basic Medical Sciences, Peking University, Beijing, People’s Republic of China
* These authors have contributed equally to this work
Correspondence to:
Li Shen, email:
Fan Wang, email:
Keywords: adoptive immunotherapy, avidin-CAR, biotinylated, EGFRvIII, optical imaging
Received: February 17, 2015 Accepted: May 31, 2015 Published: June 08, 2015
Abstract
There has been significant progress in the design of chimeric antigen receptors (CAR) for adoptive immunotherapy targeting tumor-associated antigens. However, the challenge of monitoring the therapy in real time has been continually ignored. To address this issue, we developed optical molecular imaging approaches to evaluate a recently reported novel CAR strategy for adoptive immunotherapy against glioma xenografts expressing EGFRvIII. We initially biotinylated a novel anti-EGFRvIII monoclonal antibody (biotin-4G1) to pre-target EGFRvIII+ gliomas and then redirect activated avidin-CAR expressing T cells against the pre-targeted biotin-4G1. By optical imaging study and bio-distribution analysis, we confirmed the specificity of pre-target and target and determined the optimal time for T cells adoptive transfer in vivo. The results showed this therapeutic strategy offered efficient therapy effect to EGFRvIII+ glioma-bearing mice and implied that optical imaging is a highly useful tool in aiding in the instruction of clinical CAR-T cells adoptive transfer in future.
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