A novel HLA-A2-restricted CTL epitope of tumor-associated antigen L6 can inhibit tumor growth in vivo

Shih Hsin Tu, Hsing I. Huang, Su I. Lin, Hsin Yu Liu, Yuh Pyng Sher, Sheng Kuo Chiang, Pele Chong, Steve Roffler, Guan Chin Tseng, Hsin Wei Chen, Shih Jen Liu

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Vaccines utilizing cytotoxic T lymphocyte (CTL) epitopes are promising for the treatment of cancer and chronic infectious diseases. Tumor-associated antigen L6 (TAL6) is overexpressed in some epithelial cancer cells. In this report, we detected TAL6 expression in breast cancer tissue using quantitative reverse-transcriptase-polymerase chain reaction. We found that >80% of breast tumor tissue highly expressed TAL6 compared with adjacent normal breast tissue. To identify CTL epitopes from TAL6, we synthesized 18 peptides for HLA-A2-binding assay based on the MHC-binding motif using 4 computer prediction programs. Positive binders identified by ELISA were immunized in HLA-A2 transgenic (A2 Tg) mice. Two peptides, peptide 2 and peptide 5, induced T-cell responses in A2 Tg mice. To confirm whether these peptides could be processed and presented to induce T-cell responses in vivo, A2 Tg mice were immunized with plasmid DNA encoding TAL6. We found that both peptides 2 and 5 stimulated splenocytes from TAL6-immunized mice to secrete interferon-γ. However, only peptide 5 could induce expression of the cytolytic molecule CD107a on CD8 + T cells after immunization. Furthermore, peptide 5-immunized A2 Tg mice could inhibit the growth of TAL6-positive tumors (EL4/TAL6/HLA-A2) in A2 Tg mice but not in wild-type mice. These results demonstrate that the TAL6-derived CTL epitope could induce HLA-A2-restricted immunity against TAL6-expressing tumor cells.

Original languageEnglish
Pages (from-to)235-244
Number of pages10
JournalJournal of Immunotherapy
Volume35
Issue number3
DOIs
Publication statusPublished - Apr 2012

Keywords

  • cytotoxic T lymphocytes
  • peptide
  • TAL6

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Cancer Research
  • Pharmacology

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  • Cite this

    Tu, S. H., Huang, H. I., Lin, S. I., Liu, H. Y., Sher, Y. P., Chiang, S. K., Chong, P., Roffler, S., Tseng, G. C., Chen, H. W., & Liu, S. J. (2012). A novel HLA-A2-restricted CTL epitope of tumor-associated antigen L6 can inhibit tumor growth in vivo. Journal of Immunotherapy, 35(3), 235-244. https://doi.org/10.1097/CJI.0b013e318248f2ae