Modification of the HER2/neu-derived tumor antigen GP2 improves induction of GP2-reactive cytotoxic T lymphocytes

Yoshiyuki Tanaka, Keith D. Amos, Hong Gu Joo, Timothy J. Eberlein, Peter S. Goedegebuure

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24 Scopus citations


GP2 (IISAVVGIL), the p654-662 HER2/neu-derived tumor antigen, induces HLA-A2-restricted cytotoxic T lymphocytes (CTL) reactive to various epithelial cancers. The binding affinity of GP2 for HLA-A2, however, is very low. To improve the immunogenicity of GP2, we tested 10 different amino acid substitutions into GP2 at the C- and N-terminus. Five out of 10 modified peptides, especially those containing phenylalanine at position 1 (IF), showed a significantly improved binding affinity to HLA-A2. IF-based modified peptides were well recognized by GP2-specific CTL. These peptides were used to stimulate peripheral blood lymphocytes from HLA-A2 healthy donors using peptide-pulsed autologous dendritic cells (DC). After 3 or more weekly stimulations, CTL activity against GP2 pulsed T2 (T2-GP2) and HER2/neu-overexpressing tumor cells was measured in 51Cr release and IFN-γ secretion assays. The modified peptides significantly enhanced GP2-specific CTL activity in some donors. In particular, the peptide with phenylalanine at position 1, leucine at position 2 and valine at position 10 (1F2L1OV) maximized the CTL activity against both T2-GP2 and HER2/neu-positive tumor cells. Peptide 1F2L1OV increased not only the binding affinity to HLA-A2 but also improved recognition of GP2. These data suggest that DC + modified GP2 may improve immune therapies for the treatment of HER2/neu overexpressing tumors.

Original languageEnglish
Pages (from-to)540-544
Number of pages5
JournalInternational Journal of Cancer
Issue number4
StatePublished - Nov 15 2001


  • Binding affinity
  • CTL
  • GP2
  • HLA-A*0201
  • Modification
  • Peptide recognition


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