Tumor-derived heat shock protein chaperones tumor-antigenic peptides

A. Hizuta, T. Ishii, Y. Morimoto, T. Yamano, Toshiyoshi Fujiwara, Heiichiro Udono, E. Nakayama, N. Tanaka

Research output: Contribution to journalArticle

Abstract

Heat shock proteins (HSPs) facilitate intracellular translocation of antigenic peptides as chaperones and play an essential role in antigen processing and presentation. Tumor-derived HSPs function as tumor rejection antigens to induce tumor-specific transplantation resistance. To determine if tumor-derived HSPs chaperone tumor-antigenic peptides, we purified hsp70, gp96 and hsp90 from mouse radiation-induced leukemia RL ♂ 1 and dissociated peptides from the HSPs. Tandem mass spectrometry of the dissociated peptide fractions with which RL ♂ 1-specificity CTL, Y-15 exhibited cytotoxicity against peptide-pulsed P815 revealed that hsp70 was associated with a known tumor-rejection-antigenic peptide, pRL1a, gp96 was associated with pRL1 and its precursor peptide, pRL1b, and hsp90 was associated with pRL1, pRL1b and other unknown antigenic peptide. Hsp70 and gp96 purified from surgically resected human colon cancer strongly stimulated autologous peripheral blood mononuclear cells for the production of interferon γ, tumor necrosis factor α and proliferative responses. The cytotoxicity of tumor-specific cytotoxic T lymphocytes was also induced by the culture with the hsp70. These results suggest that the autologous cancer-derived HSP, which is associated with both known and unknown tumor-antigenic peptides, is an effective tumor vaccine for the immunotherapy of cancers without the HLA haplotype restriction.

Original languageEnglish
Pages (from-to)573-575
Number of pages3
JournalBiotherapy
Volume12
Issue number5
Publication statusPublished - 1998

Fingerprint

Heat-Shock Proteins
Peptides
Neoplasms
Antigen Presentation
Radiation-Induced Leukemia
Cancer Vaccines
Cytotoxic T-Lymphocytes
Neoplasm Antigens
Tandem Mass Spectrometry
Immunotherapy
Colonic Neoplasms
Haplotypes
Interferons
Blood Cells
Tumor Necrosis Factor-alpha
Transplantation

Keywords

  • Chaperone
  • Gp96
  • Heat shock protein
  • Hsp70
  • Hsp90
  • Tumor vaccine

ASJC Scopus subject areas

  • Cancer Research
  • Immunology and Allergy

Cite this

Hizuta, A., Ishii, T., Morimoto, Y., Yamano, T., Fujiwara, T., Udono, H., ... Tanaka, N. (1998). Tumor-derived heat shock protein chaperones tumor-antigenic peptides. Biotherapy, 12(5), 573-575.

Tumor-derived heat shock protein chaperones tumor-antigenic peptides. / Hizuta, A.; Ishii, T.; Morimoto, Y.; Yamano, T.; Fujiwara, Toshiyoshi; Udono, Heiichiro; Nakayama, E.; Tanaka, N.

In: Biotherapy, Vol. 12, No. 5, 1998, p. 573-575.

Research output: Contribution to journalArticle

Hizuta, A, Ishii, T, Morimoto, Y, Yamano, T, Fujiwara, T, Udono, H, Nakayama, E & Tanaka, N 1998, 'Tumor-derived heat shock protein chaperones tumor-antigenic peptides', Biotherapy, vol. 12, no. 5, pp. 573-575.
Hizuta A, Ishii T, Morimoto Y, Yamano T, Fujiwara T, Udono H et al. Tumor-derived heat shock protein chaperones tumor-antigenic peptides. Biotherapy. 1998;12(5):573-575.
Hizuta, A. ; Ishii, T. ; Morimoto, Y. ; Yamano, T. ; Fujiwara, Toshiyoshi ; Udono, Heiichiro ; Nakayama, E. ; Tanaka, N. / Tumor-derived heat shock protein chaperones tumor-antigenic peptides. In: Biotherapy. 1998 ; Vol. 12, No. 5. pp. 573-575.
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