Identification of HLA-A3-restricted cytotoxic T lymphocyte epitopes from carcinoembryonic antigen and HER-2/neu by primary in vitro immunization with peptide-pulsed dendritic cells

Ichiro Kawashima, Van Tsai, Scott Southwood, Kazutoh Takesako, Alessandro Sette, Esteban Celis

Research output: Contribution to journalArticlepeer-review

121 Scopus citations

Abstract

The human carcinoembryonic antigen (CEA) and HER-2/neu are potential target antigens for CTL specific immunotherapy for common malignancies such as breast, lung, colon, and gastric carcinomas. Several CTL epitopes restricted by HLA-A2, the most common human histocompatibility molecule, have been previously reported. However, to develop CTL-based immunotherapies for the general population, it is necessary to identify epitopes restricted by other common histocompatibility alleles. Here, we describe two HLA-A3- restricted CTL epitopes from the CEA and HER-2/neu antigens. HLA-A3 binding synthetic peptides from CEA and HER-2/neu were tested for immunogenicity by in vitro primary CTL induction protocol using peripheral blood mononuclear cells from normal healthy volunteers. One peptide from CEA (CEA[961]: HLFGYSWYK) and one peptide from HER-2/neu (HER2[9754]: VLRENTSPK) were shown to induce CTL that was capable of killing a tumor cell line expressing HLA-A3 and the corresponding tumor-associated antigen. Additional MHC binding studies with the most common HLA molecules belonging to the HLA-A3 superfamily (HLA-A*1101, -A*3101, -A*3301, and -A*6801), demonstrated that CEA[961] binds five of five A3 supertype molecules with high affinity, and the HER2[9754] epitope was able to bind to four of the same five alleles. These results indicate that these two new CTL epitopes should be immunogenic in individuals expressing either HLA-A3, or other members of the HLA-A3 superfamily.

Original languageEnglish (US)
Pages (from-to)431-435
Number of pages5
JournalCancer Research
Volume59
Issue number2
StatePublished - Jan 16 1999
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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