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Targeting the epidermal growth factor receptor (HER) family by T cell receptor gene-modified T lymphocytes

Item Type:Article
Title:Targeting the epidermal growth factor receptor (HER) family by T cell receptor gene-modified T lymphocytes
Creators Name:Meyerhuber, P., Conrad, H., Staerck, L., Leisegang, M., Busch, D.H., Uckert, W. and Bernhard, H.
Abstract:Human epidermal growth factor receptor 2 (HER2) has been successfully targeted as a breast cancer-associated antigen by various strategies. HER2 is also overexpressed in other solid tumors such as stomach cancer, as well as in hematological malignancies such as acute lymphoblastic leukemia. HER2-targeted therapies are currently under clinical investigation for a panel of malignancies. In this study, we isolated the T cell receptor (TCR) genes of a HER2-reactive allo-human leukocyte antigen-A2-restricted CTL clone and introduced the TCRalpha- and beta-chain genes into the retrovirus vector MP71. Murinization and codon optimization of the HER2-reactive TCR was required for efficient TCR expression in primary human T cells. The tumor recognition efficiency of HER2-TCR gene-modified T cells was similar to the parental CTL clone from which the TCR genes were isolated. The known cross-reactivity of the HER2-reactive TCR with HER3 and HER4 was retained when the TCR was transduced into primary T cells. Our results could contribute to the development of a TCR-based approach for the treatment of HER2-positive breast cancer, as well as of other malignancies expressing HER2, HER3, and/or HER4.
Keywords:Adoptive T Cell Therapy, TCR Gene Transfer, HER2-TCR, Retroviral Vector, ErbB2, HER2
Source:Journal of Molecular Medicine
Page Range:1113-1121
Date:November 2010
Official Publication:https://doi.org/10.1007/s00109-010-0660-z
PubMed:View item in PubMed

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