Generation of RAGE‐1 and MAGE‐9 peptide‐specific cytotoxic T‐Lymphocyte lines for transfer in patients with renal cell carcinoma

Renal cell carcinomas (RCCs) are supposed to be immunogenic, and several clinical trials of immunotherapy using tumor lysate‐pulsed dendritic cells (DCs) have been performed. We report on the generation of RAGE‐1 and MAGE‐9 peptide‐specific CTL lines. RAGE‐1 and MAGE‐9 are expressed in 56% and 38% o...

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Bibliographic Details
Published in:	International journal of cancer Vol. 117; no. 2; pp. 256 - 264
Main Authors:	Oehlrich, Nicole, Devitt, Gerard, Linnebacher, Michael, Schwitalle, Yvette, Groβkinski, Sonja, Stevanovic, Stefan, Zöller, Margot
Format:	Journal Article
Language:	English
Published:	Hoboken Wiley Subscription Services, Inc., A Wiley Company 01-11-2005 Wiley-Liss
Subjects:	Adoptive Transfer Amino Acid Sequence Antigens, Neoplasm - genetics antigen‐presenting cell Antineoplastic agents B-Lymphocytes - immunology Biological and medical sciences Carcinoma, Renal Cell - genetics Carcinoma, Renal Cell - immunology Cytotoxicity, Immunologic HLA-A Antigens - genetics HLA-A2 Antigen human renal cell carcinoma Humans Immunotherapy Major Histocompatibility Complex Medical sciences Mitogen-Activated Protein Kinases - genetics Peptide Fragments - chemistry peptide‐specific cytotoxic T lymphocyte Pharmacology. Drug treatments T-Lymphocytes, Cytotoxic - immunology Tumors Kidney disease Antineoplastic agent Human Nephrology Urinary system disease Carcinoma Tumor associated antigen Peptides antigen-presenting cell RAGE 1 antigen B-Lymphocyte Malignant tumor peptide-specific cytotoxic T lymphocyte Urology Cancerology Treatment Antigen presenting cell Immunotherapy Grawitz tumor Adoptive immunization Cytotoxic T lymphocyte human renal cell carcinoma
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Summary:	Renal cell carcinomas (RCCs) are supposed to be immunogenic, and several clinical trials of immunotherapy using tumor lysate‐pulsed dendritic cells (DCs) have been performed. We report on the generation of RAGE‐1 and MAGE‐9 peptide‐specific CTL lines. RAGE‐1 and MAGE‐9 are expressed in 56% and 38% of RCCs. Seven MAGE‐9‐ and 13 RAGE‐1‐derived peptides were found to be immunogenic in the context of the HLA‐A0201 MHC. CTLs were generated by coculture with peptide‐pulsed, activated B cells, which were easily generated in great quantities and displayed functional activity for a prolonged period of time. MAGE‐9 and RAGE‐1 peptide‐specific CTL lines were strictly peptide‐specific and displayed high cytotoxic activity not only against peptide‐loaded T2 cells but also against HLA‐A0201‐positive RCC lines, which naturally express MAGE‐9, RAGE‐1 or both. Thus, B cells are well suited as APCs for the generation of large numbers of tumor peptide‐specific CTLs for adoptive transfer. MAGE‐9 as well as RAGE‐1 may well provide suitable targets for immunotherapy of RCC. © 2005 Wiley‐Liss, Inc.
Bibliography:	Fax: +49‐6221‐424760. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0020-7136 1097-0215
DOI:	10.1002/ijc.21200