PuSH - Publication Server of Helmholtz Zentrum München: Gene transfer of human interferon gamma complementary DNA into a renal cell carcinoma line enhances MHC-restricted cytotoxic T lymphocyte recognition but suppresses non-MHC-restricted effector cell activity.

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Schendel, D.J. ; Falk, C.S. ; Nößner, E. ; Maget, B. ; Kressenstein, S. ; Urlinger, S.* ; Tampé, R.* ; Gansbacher, B.*

Gene transfer of human interferon gamma complementary DNA into a renal cell carcinoma line enhances MHC-restricted cytotoxic T lymphocyte recognition but suppresses non-MHC-restricted effector cell activity.

Gene Ther. 7, 2-10 (2000)

Open Access Green as soon as Postprint is submitted to ZB.

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ven though renal cell carcinomas (RCC) are thought to be immunogenic, many tumors express variations in surface molecules and intracellular proteins that hinder induction of optimal antitumor responses. Interferon gamma (IFN gamma) stimulation can correct some of these deficiencies. Therefore, we introduced the complementary DNA (cDNA) encoding human IFN gamma into a well-characterized RCC line that has been selected for development of an allogeneic tumor cell vaccine for treatment of patients with metastatic disease. Studies were performed to determine how endogenous IFN gamma expression influences tumor cell immunogenicity. IFN gamma transductants showed minimal increases in surface expression of MHC class I and adhesion molecules but expression of class Ii molecules was induced. Proteins of the transporter associated with antigen processing (TAP) and low molecular weight polypeptide (LMP) were constitutively expressed at high levels. The transductants stimulated allospecific cytotoxic T lymphocytes (CTL); however, they were not better than unmodified tumor cells in this capacity. Endogenous IFN gamma expression enhanced tumor cell recognition by MHC-restricted, tumor antigen-specific CTL but suppressed recognition by non-MHC-restricted cytotoxic cells. Thus, the functional consequences of IFN gamma expression varied with respect to the type of effector cell and were not always beneficial for tumor cell recognition.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords interferon-gamma; allogeneic vaccine; renal cell carcinoma

ISSN (print) / ISBN 0969-7128

e-ISSN 1476-5462

Journal Gene Therapy

Quellenangaben Volume: 7, Pages: 2-10

Publisher Nature Publishing Group

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Molecular Immunology (IMI)