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Sci Rep. 2014 Jan 6;4:3571. doi: 10.1038/srep03571.

Anti-melanoma activity of T cells redirected with a TCR-like chimeric antigen receptor.

Author information

1
1] Chinese Academy of Sciences Key Laboratory of Pathogenic Microbiology and Immunology (CASPMI), and China-Japan Joint Laboratory of Molecular Immunology and Microbiology, Institute of Microbiology, Chinese Academy of Sciences, 100101 Beijing, China [2] University of Chinese Academy of Sciences, Beijing, China.
2
Chinese Academy of Sciences Key Laboratory of Pathogenic Microbiology and Immunology (CASPMI), and China-Japan Joint Laboratory of Molecular Immunology and Microbiology, Institute of Microbiology, Chinese Academy of Sciences, 100101 Beijing, China.
3
Beijing Hospital of Traditional Chinese Medicine affiliated to Capital Medical University, 100010 Beijing, China.
4
Hebei Key Laboratory of Medical Biotechnology, Hebei Medical University, 050017 Shijiazhuang, China.
5
Epigen Biotec Ltd, 100101 Beijing, China.

Abstract

Genetically modified T cells to recognize tumor-associated antigens by transgenic TCRs or chimeric antigen receptors (CAR) have been successfully applied in clinical trials. However, the disadvantages of either TCR mismatching or the requirement of a surface tumor antigen limit their wider applications in adoptive T cell therapy. A TCR-like chimeric receptor, specific for the melanoma-related gp100/HLA-A2 complex was created by joining a TCR-like antibody GPA7 with the endodomains of CD28 and CD3-ζ chain. This TCR-like CAR, GPA7-28z, was subsequently introduced into human T cells. Retargeted T cells expressing GPA7-28z could exhibit efficient cytotoxic activities against human melanoma cells in vitro in the context with HLA-A2. Furthermore, infusion of GPA7-28z-transduced T cells suppressed melanoma progression in a xenograft mouse model. Redirecting human T cells with TCR-like CARs would be a promising alternative approach to TCR-mediated therapy for melanoma patients, which is also feasible for targeting a variety of other tumor antigens.

PMID:
24389689
PMCID:
PMC3880964
DOI:
10.1038/srep03571
[Indexed for MEDLINE]
Free PMC Article

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