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[Cancer Research 59, 431-435, January 1, 1999]
© 1999 American Association for Cancer Research
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[Cancer Research 59, 431-435, January 15, 1999]
© 1999 American Association for Cancer Research

Immunology

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 Cells1

Ichiro Kawashima, Van Tsai, Scott Southwood, Kazutoh Takesako, Alessandro Sette and Esteban Celis2

Takara Shuzo Co., Ltd., Biotechnology Research Laboratories, Otsu, Shiga, 520-21 Japan [I. K., K. T.]; Epimmune, Inc., San Diego, California 92121 [V. T., S. S., A. S.]; and Department of Immunology, Mayo Clinic, Rochester, Minnesota 55905 [E. C.]

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.




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Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 1999 by the American Association for Cancer Research.