Regression of intestinal adenomas by vaccination with heat shock protein 105-pulsed bone marrow-derived dendritic cells in Apc(Min/+) mice.

Cancer science

PubMedID: 17892515

Yokomine K, Nakatsura T, Senju S, Nakagata N, Minohara M, Kira J, Motomura Y, Kubo T, Sasaki Y, Nishimura Y. Regression of intestinal adenomas by vaccination with heat shock protein 105-pulsed bone marrow-derived dendritic cells in Apc(Min/+) mice. Cancer Sci. 2007;98(12):1930-5.
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.