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Meyerhuber, P.* ; Conrad, H. ; Stärck, L.* ; Leisegang, M.* ; Busch, D.H. ; Uckert, W.* ; Bernhard, H.

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

J. Mol. Med. 88, 1113-1121 (2010)
Verlagsversion DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Adoptive T cell therapy; TCR gene transfer; HER2-TCR; Retroviral vector; ErbB2; HER2
ISSN (print) / ISBN 0946-2716
e-ISSN 1432-1440
Zeitschrift Journal of Molecular Medicine
Quellenangaben Band: 88, Heft: 11, Seiten: 1113-1121 Artikelnummer: , Supplement: ,
Verlag Springer
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) CCG Antigen-specific Immunotherapy (VIRO-KVA)