PuSH - Publikationsserver des Helmholtz Zentrums München

Leisegang, M.* ; Turqueti-Neves, A. ; Engels, B.* ; Blankenstein, T.* ; Schendel, D.J. ; Uckert, W.* ; Nössner, E.

T-cell receptor gene-modified T cells with shared renal cell carcinoma specificity for adoptive T-cell therapy.

Clin. Cancer Res. 16, 2333-2343 (2010)
Verlagsversion DOI PMC
Closed
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
PURPOSE: Adoptive therapy with genetically engineered T cells carrying redirected antigen specificity is a new option for the treatment of cancer. This approach is not yet available for metastatic renal cell carcinoma (RCC), due to the scarcity of therapeutically useful reagents. We analyzed tumor-infiltrating lymphocytes (TIL) from RCC to identify T-cell specificities with shared tumor-specific recognition to develop T-cell receptor (TCR)-engineered T lymphocytes for adoptive therapy of RCC. EXPERIMENTAL DESIGN: We established a T-cell clone from TIL that recognized a human leukocyte antigen (HLA)-A2-restricted tumor antigen. The TCR alpha- and beta-chain genes were isolated, modified by codon optimization and murinization, and retrovirally transduced into peripheral blood lymphocytes (PBL). A TCR-expressing indicator line (B3Z-TCR53) was established to screen for antigen prevalence in RCC, other malignancies, and normal cell counterparts. RESULTS: TCR53-engineered PBL recapitulated the specificity of the TIL and showed tumor-specific HLA-A2-restricted effector activities (IFN-gamma, tumor necrosis factor-alpha, interleukin-2, macrophage inflammatory protein-1beta, cytotoxicity). PBL-TCR53 of healthy donors and RCC patients exhibited similar transduction efficiency, expansion, and polyfunctional profile. Using B3Z-TCR53 cells, 130 tumor and normal cells were screened and shared TCR53 peptide: MHC expression was found in >60% of RCC and 25% of tumor lines of other histology, whereas normal tissue cells were not recognized. CONCLUSIONS: To date, TCR53 is the only TCR with shared HLA-A2-restricted recognition of RCC. It fulfills the criteria for utilization in TCR gene therapy and advances T cell-based immunotherapy to patients with RCC and other malignancies expressing the TCR ligand.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Scopus
Cited By
Altmetric
6.747
2.360
19
31
Tags
Anmerkungen
Besondere Publikation
Auf Hompepage verbergern

Zusatzinfos bearbeiten
Eigene Tags bearbeiten
Privat
Eigene Anmerkung bearbeiten
Privat
Auf Publikationslisten für
Homepage nicht anzeigen
Als besondere Publikation
markieren
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Tumor-infiltrating lymphocytes; Antitumor-activity; Cancer regression; Kidney cancer; In-vivo; Antigen; Expression; Immunotherapy; MHC; Transplantation
Sprache englisch
Veröffentlichungsjahr 2010
HGF-Berichtsjahr 2010
ISSN (print) / ISBN 1078-0432
e-ISSN 1557-3265
Quellenangaben Band: 16, Heft: 8, Seiten: 2333-2343 Artikelnummer: , Supplement: ,
Verlag American Association for Cancer Research (AACR)
Begutachtungsstatus Peer reviewed
POF Topic(s) 30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Forschungsfeld(er) Immune Response and Infection
PSP-Element(e) G-501700-001
G-501790-001
G-501700-005
G-520400-001
G-501700-002
PubMed ID 20371691
Scopus ID 77950991814
Erfassungsdatum 2010-11-30