Identification of new HER2/neu-derived peptide epitopes that can elicit specific CTL against autologous and allogeneic carcinomas and melanomas

Yang Rongcun, Flavio Salazar-Onfray, Jehad Charo, Karl Johan Malmberg, Kristina Evrin, Hubert Maes, Koji Kono, Christina Hising, Max Petersson, Olle Larsson, Li Lan, Ettore Appella, Alessandro Sette, Esteban Celis, Rolf Kiessling

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164 Scopus citations

Abstract

Twenty-two new HLA-A2. 1-binding peptides derived from the protooncogene HER2/neu were identified and analyzed for their capacity to elicit peptide and tumor-specific CTL responses. We used peptide-pulsed autologous DC from the ascites of patients with ovarian carcinomas to induce CTL. Of the 22 tested new HER2/neu-derived epitopes that could bind HLA-A2 with high (IC50 < 50 nM) or intermediate (50 nM< IC50 < 500 nM) affinity, we report the recognition by CTL of at least four novel epitopes, including HER2(9435), HER2(9665), HER2(9689), and HER2(10952), and confirm that of the known HER2 (9369) epitope. These epitopes were able to elicit CTI, that specifically killed peptide-sensitized target cells and, most importantly, a HER2/neu-transfected cell line and the autologous tumor cells. We also confirm that HER2/neu is overexpressed in several melanoma lines, and as a new finding, report that some of these lines are sensitive to CTL induced by the HER2 (9369), HER2(9435), and HER2(9689) epitopes. Finally, CTL clones specific for HER2 (9369), HER2(9435), and HER2(9689) epitopes were isolated from tumor-specific CTL lines, further demonstrating the immunodominance of these epitopes. These findings broaden the potential application of HER2/neu-based immunotherapy.

Original languageEnglish (US)
Pages (from-to)1037-1044
Number of pages8
JournalJournal of Immunology
Volume163
Issue number2
StatePublished - Jul 15 1999

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Rongcun, Y., Salazar-Onfray, F., Charo, J., Malmberg, K. J., Evrin, K., Maes, H., Kono, K., Hising, C., Petersson, M., Larsson, O., Lan, L., Appella, E., Sette, A., Celis, E., & Kiessling, R. (1999). Identification of new HER2/neu-derived peptide epitopes that can elicit specific CTL against autologous and allogeneic carcinomas and melanomas. Journal of Immunology, 163(2), 1037-1044.