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

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.

• Authors: Ge Zhang, Lei Wang, Honglian Cui, Xiaomin Wang, Ganlin Zhang, Juan Ma, Huamin Han, Wen He, Wei Wang, Yunfeng Zhao, Changzhen Liu, Meiyi Sun, Bin Gao
• Journal: Scientific reports (Sci Rep) Vol. 4 Pg. 3571 (Jan 06 2014) ISSN: 2045-2322 [Electronic] England
• PMID: 24389689 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Receptors, Antigen, T-Cell
• Recombinant Fusion Proteins

Topics

• Animals
• Cells, Cultured
• Female
• Humans
• Melanoma (immunology, pathology)
• Mice
• Mice, SCID
• Receptors, Antigen, T-Cell (immunology)
• Recombinant Fusion Proteins (immunology)
• T-Lymphocytes (immunology)
• Tumor Cells, Cultured