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

Int J Cancer. 2005 Nov 1;117(2):256-64. doi: 10.1002/ijc.21200.

Abstract

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-A*0201 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-A*0201-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Amino Acid Sequence
  • Antigens, Neoplasm / genetics*
  • B-Lymphocytes / immunology
  • Carcinoma, Renal Cell / genetics
  • Carcinoma, Renal Cell / immunology*
  • Cytotoxicity, Immunologic
  • HLA-A Antigens / genetics
  • HLA-A2 Antigen
  • Humans
  • Major Histocompatibility Complex
  • Mitogen-Activated Protein Kinases / genetics*
  • Peptide Fragments / chemistry
  • T-Lymphocytes, Cytotoxic / immunology*

Substances

  • Antigens, Neoplasm
  • HLA-A Antigens
  • HLA-A*02:01 antigen
  • HLA-A2 Antigen
  • MAGE-9 antigen, human
  • Peptide Fragments
  • MOK protein, human
  • Mitogen-Activated Protein Kinases