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A gene encoding antigenic peptides of human squamous cell carcinoma recognized by cytotoxic T lymphocytes

S Shichijo1, M Nakao, Y Imai

  • 1Department of Immunology, Kurume University School of Medicine, Kurume, Japan.

The Journal of Experimental Medicine
|March 21, 1998
PubMed

Insights

Researchers identified a novel gene encoding tumor antigens in squamous cell carcinomas (SCCs) recognized by specific T cells. A 43-kD protein and a nonapeptide may offer new avenues for epithelial cancer immunotherapy.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Identifying tumor antigens for T-cell recognition is crucial for cancer immunotherapy, especially for cytotoxic T lymphocytes (CTLs).
  • Antigens for CTL recognition remain largely unknown, except in melanomas, hindering the development of targeted cancer therapies.

Purpose of the Study:

  • To identify and characterize novel tumor antigens in human squamous cell carcinomas (SCCs) recognized by human histocompatibility leukocyte antigen (HLA)-A2601-restricted CTLs.
  • To evaluate the potential of identified antigens for specific cancer immunotherapy.

Main Methods:

  • Gene identification and sequence analysis.
  • Protein expression analysis in various normal and malignant tissues using immunoblotting.
  • Peptide identification and T-cell recognition assays using CTLs and peripheral blood mononuclear cells (PBMCs).

Main Results:

  • A novel gene encoding 125-kD and 43-kD proteins was identified in SCCs.
  • The 43-kD protein was specifically expressed in most SCCs and some lung adenocarcinomas, but not in other cancers or normal tissues.
  • Three shared nonapeptides were recognized by KE4 CTLs, and one peptide induced autologous tumor-specific CTLs from PBMCs.

Conclusions:

  • The 43-kD protein and its associated nonapeptide (KGSGKMKTE) are potential tumor-specific antigens for HLA-A2601-positive epithelial cancers.
  • These findings suggest a promising strategy for developing specific immunotherapies for SCCs and potentially other epithelial cancers.

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