HER2-Specific T-Cell Immune Responses in Patients Vaccinated with Truncated HER2 Protein Complexed with Nanogels of Cholesteryl Pullulan Academic Article uri icon

abstract

  • PURPOSE: We developed a complex of tumor antigen protein with a novel nanoparticle antigen delivery system of cholesteryl pullulan (CHP). To target HER2 antigen, we prepared truncated HER2 protein 1-146 (146HER2) complexed with CHP, the CHP-HER2 vaccine. We designed a clinical study to assess the safety of the vaccine and HER2-specific T-cell immune responses measured by the newly developed enzyme-linked immunospot assay with mRNA-transduced phytohemagglutinin-stimulated CD4(+) T cells in HLA-A2402-positive patients with therapy-refractory HER2-expressing cancers. EXPERIMENTAL DESIGN: Nine patients with various types of solid tumors were enrolled. Each patient was s.c. vaccinated biweekly with 300 microg of CHP-HER2 vaccine for three times followed by booster doses. HER2-specific T-cell responses were evaluated by enzyme-linked immunospot assay by targeting autologous phytohemagglutinin-stimulated CD4(+) T cells transduced with 146HER2-encoding mRNA to cover both identified peptides and unknown epitopes for MHC class I and class II that might exist in the sequence of the vaccine protein. RESULTS: CHP-HER2 vaccine was well tolerated; the only adverse effect was grade 1 transient skin reaction at the sites of vaccination. HER2-specific CD8(+) and/or CD4(+) T-cell immune responses were detected in five patients who received four to eight vaccinations, among whom both T-cell responses were detected in these patients. In four patients with CD8(+) T-cell responses, two patients reacted to previously identified HER2(63-71) peptide and the other two reacted only to 146HER2 mRNA-transduced cells. CONCLUSIONS: CHP-HER2 vaccine was safe and induced HER2-specific CD8(+) and/or CD4(+) T-cell immune responses.

authors

  • Kitano, S
  • Kageyama, S
  • Nagata, Y
  • Miyahara, Y
  • Hiasa, A
  • Naota, H
  • Okumura, S
  • Imai, H
  • Shiraishi, T
  • Masuya, M
  • Nishikawa, M
  • Sunamoto, J
  • Akiyoshi, K
  • Kanematsu, T
  • Scott, AM
  • Murphy, R
  • Hoffman, EW
  • Old, LJ
  • Shiku, H

publication date

  • December 15, 2006