Induction of antigen specific cellular immunity by vaccination with peptides from MN/CA IX in renal cell carcinoma

Oncol Rep. 2003 Sep-Oct;10(5):1307-11.

Abstract

We investigated the induction of the specific immunity for renal cell carcinomas (RCC) using MN/CA IX, a tumor-associated antigen frequently expressed in RCC. We have generated 9-mer peptide derived from MN/CA IX and examined the antigenicity as a vaccine to induce specific immunity for RCC. To use mouse syngeneic system, we transfected human MN/CA9 cDNA into RenCa and BALB-3T3 cells originally from BALB/c mouse, and established MN/CA IX expressing mouse cell lines, i.e., MN-RenCa and MN-3T3. The immunization of BALB/c mouse with MN-RenCa cells resulted in the induction of cytotoxic T lymphocytes (CTL) against MN/CA IX expressing cells and the CTL clone was established from bulked CTL. This CTL clone specifically lyzed MN-3T3 cells, but not parental cells. To identify the targeted epitope binding to H-2Kd antigen, three 9-mer peptides (A, B, C-peptide) of human MN/CA IX compatible with the H-2Kd as well as HLA-A24 binding motif was synthesized. The cloned CTL targeted the B-peptide pulsed BALB-3T3 cells as well as MN-3T3 cells. Furthermore, spleen cells from BALB/c mouse immunized with B-peptide reacted against MN-RenCa cells. These results suggest that the peptides derived from MN/CA IX containing HLA-A24 binding motif may be useful as a potent tumor vaccine for the treatment of human RCC, and in mouse models.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Neoplasm / biosynthesis*
  • Antigens, Neoplasm / chemistry
  • Cancer Vaccines*
  • Carbonic Anhydrase IX
  • Carbonic Anhydrases / biosynthesis*
  • Carcinoma, Renal Cell / prevention & control*
  • Carcinoma, Renal Cell / therapy*
  • Cell Line
  • DNA, Complementary / metabolism
  • Epitopes / chemistry
  • Female
  • Fibroblasts / metabolism
  • Flow Cytometry
  • Humans
  • Kidney Neoplasms / prevention & control*
  • Kidney Neoplasms / therapy*
  • Mice
  • Mice, Inbred BALB C
  • NIH 3T3 Cells
  • Neoplasm Proteins / biosynthesis*
  • Peptides / chemistry
  • Phenotype
  • Plasmids / metabolism
  • Protein Binding
  • Spleen / cytology
  • T-Lymphocytes, Cytotoxic / metabolism
  • Transfection

Substances

  • Antigens, Neoplasm
  • Cancer Vaccines
  • DNA, Complementary
  • Epitopes
  • Neoplasm Proteins
  • Peptides
  • CA9 protein, human
  • Carbonic Anhydrase IX
  • Carbonic Anhydrases