In Vitro Generation of Human Cytolytic T-Cells Specific for Peptides Derived from the HER-2/neu Protooncogene Protein

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作者：

ML Disis，JW Smith，AE Murphy，W Chen，MA Cheever

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摘要：

The development of T-cell therapy for the treatment of human malignancy has been hindered, in large part, by a lack of identifiable tumor antigens. Studies to identify potential T-cell targets in humans have been difficult because of practical problems limiting the use of in vivo immunization and a lack of reproducible in vitro priming methods. Oncogenic proteins are involved in malignant transformation and maintenance of the transformed phenotype and theoretically are potential targets to T-cell therapy. HER-2/neu protein is a protooncogene product overexpressed in a variety of human malignancies and is associated with malignant transformation and aggressive disease in human breast cancer. Previous studies have shown that some patients with breast cancer have existent helper/inducer T-cell immunity to p185HER-2/neu protein and peptides. The current study represents initial attempts to identify candidate cytotoxic T-lymphocyte (CTL) epitopes. Synthetic peptides were constructed identical to HER-2/neu protein segments with amino acid motifs similar to the published motif for HLA-2.1-binding peptides. Four peptides were synthesized and two were shown to be avid binders to HLA-A2.1. Two of the four peptides could be shown to elicit peptide-specific CTL by primary in vitro immunization in a culture system using peripheral blood lymphocytes from a normal individual homozygous for HLA-A2. p185HER-2/neu protooncogene protein contains immunogenic epitopes capable of generating human CD8+ CTL. The identification of candidate CTL epitopes will allow studies to determine whether some cancer patients have existent CTL immunity to HER-2/neu protein. The demonstrated ability to generate human peptide-specific CTL in vitro allows screening of other oncogenic proteins to identify candidate T-cell epitopes potentially useful for future immunotherapy studies.

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关键词：

SMALL ROUND CELL TUMOR INSULIN-LIKE GROWTH FACTOR II INSULIN-LIKE GROWTH FACTOR I RECEPTORS IGF-II/MANNOSE 6-PHOSPHATE RECEPTORS

DOI：

doi:10.1002/1097-0142(19940215)73:4<1312::AID-CNCR2820730429>3.0

被引量：

773

年份：

1994