Regression of intestinal adenomas by vaccination with heat shock protein 105-pulsed bone marrow-derived dendritic cells in Apc(Min/+) mice.
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 Apc(Min/+) 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 Apc(Min/+) mouse. Western blot and immunohistochemical analyses revealed that the tumors of the Apc(Min/+) mice endogenously overexpressed HSP105. Immunization of the Apc(Min/+) 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 Apc(Min/+) mouse model.
Yokomine
Kazunori
K
Departments of Immunogenetics, and Gastroenterology and Hepatology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-08556, Japan.
Nakatsura
Tetsuya
T
Senju
Satoru
S
Nakagata
Naomi
N
Minohara
Motozumi
M
Kira
Jun-Ichi
J
Motomura
Yutaka
Y
Kubo
Tatsuko
T
Sasaki
Yutaka
Y
Nishimura
Yasuharu
Y
D000236:Adenoma / Q000276:immunology*; D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines; D003713:Dendritic Cells / Q000276:immunology*; D017353:Gene Deletion; D017491:Genes, APC; D005838:Genotype; D050957:HSP110 Heat-Shock Proteins / Q000235:genetics / Q000276:immunology*; D007414:Intestinal Neoplasms / Q000276:immunology*; D007417:Intestinal Polyps / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL / Q000235:genetics
D019496:Cancer Vaccines; D050957:HSP110 Heat-Shock Proteins; C490783:Hsp105 protein, mouse