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Targeting the epidermal growth factor receptor (HER) family by T cell receptor gene-modified T lymphocytes.
J. Mol. Med. 88, 1113-1121 (2010)
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.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Adoptive T cell therapy; TCR gene transfer; HER2-TCR; Retroviral vector; ErbB2; HER2
ISSN (print) / ISBN
0946-2716
e-ISSN
1432-1440
Journal
Journal of Molecular Medicine
Quellenangaben
Volume: 88,
Issue: 11,
Pages: 1113-1121
Publisher
Springer
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
CCG Antigen-specific Immunotherapy (VIRO-KVA)