Regression of intestinal adenomas by vaccination with heat shock protein 105-pulsed bone marrow-derived dendritic cells in ApcMin/+ mice

Kazunori Yokomine, Tetsuya Nakatsura, Satoru Senju, Naomi Nakagata, Motozumi Minohara, Jun-Ichi Kira, Yutaka Motomura, Tatsuko Kubo, Yutaka Sasaki, Yasuharu Nishimura

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Heat shock protein (HSP) 105 is overexpressed in various cancers, but is expressed at low levels in many normal tissues, except for the testis. A vaccination with HSP105-pulsed bone marrow-derived dendritic cells (BM-DC) induced antitumor immunity without causing an autoimmune reaction in a mouse model. Because ApcMin/+ mice develop multiple adenomas throughout the intestinal tract by 4 months of age, the mice provide a clinically relevant model of human intestinal tumor. In the present study, we investigated the efficacy of the HSP105-pulsed BM-DC vaccine on tumor regression in the ApcMin/+ mouse. Western blot and immunohistochemical analyses revealed that the tumors of the ApcMin/+ mice endogenously overexpressed HSP105. Immunization of the ApcMin/+ mice with a HSP105-pulsed BM-DC vaccine at 6, 8, and 10 weeks of age significantly reduced the number of small-intestinal polyps accompanied by infiltration of both CD4+ and CD8+ T cells in the tumors. Cell depletion experiments proved that both CD4+ and CD8+ T cells play a critical role in the activation of antitumor immunity induced by these vaccinations. These findings indicate that the HSP105-pulsed BM-DC vaccine can provide potent immunotherapy for tumors that appear spontaneously as a result of the inactivation of a tumor suppressor gene, such as in the ApcMin/+ mouse model.

Original languageEnglish
Pages (from-to)1930-1935
Number of pages6
JournalCancer Science
Volume98
Issue number12
DOIs
Publication statusPublished - Dec 1 2007

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Heat-Shock Proteins
Adenoma
Dendritic Cells
Vaccination
Bone Marrow
Neoplasms
Immunity
Intestinal Polyps
Vaccines
T-Lymphocytes
Cancer Vaccines
Tumor Suppressor Genes
Immunotherapy
Testis
Immunization
Western Blotting

All Science Journal Classification (ASJC) codes

  • Cancer Research
  • Oncology

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Regression of intestinal adenomas by vaccination with heat shock protein 105-pulsed bone marrow-derived dendritic cells in ApcMin/+ mice. / Yokomine, Kazunori; Nakatsura, Tetsuya; Senju, Satoru; Nakagata, Naomi; Minohara, Motozumi; Kira, Jun-Ichi; Motomura, Yutaka; Kubo, Tatsuko; Sasaki, Yutaka; Nishimura, Yasuharu.

In: Cancer Science, Vol. 98, No. 12, 01.12.2007, p. 1930-1935.

Research output: Contribution to journalArticle

Yokomine, K, Nakatsura, T, Senju, S, Nakagata, N, Minohara, M, Kira, J-I, Motomura, Y, Kubo, T, Sasaki, Y & Nishimura, Y 2007, 'Regression of intestinal adenomas by vaccination with heat shock protein 105-pulsed bone marrow-derived dendritic cells in ApcMin/+ mice', Cancer Science, vol. 98, no. 12, pp. 1930-1935. https://doi.org/10.1111/j.1349-7006.2007.00612.x
Yokomine, Kazunori ; Nakatsura, Tetsuya ; Senju, Satoru ; Nakagata, Naomi ; Minohara, Motozumi ; Kira, Jun-Ichi ; Motomura, Yutaka ; Kubo, Tatsuko ; Sasaki, Yutaka ; Nishimura, Yasuharu. / Regression of intestinal adenomas by vaccination with heat shock protein 105-pulsed bone marrow-derived dendritic cells in ApcMin/+ mice. In: Cancer Science. 2007 ; Vol. 98, No. 12. pp. 1930-1935.
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