Anti-TGF-β antibody combined with dendritic cells produce antitumor effects in osteosarcoma.

Abstract

We previously reported the combination of tumor cryotreatment with dendritic cells to promote antitumor immunity. The effect of the combination treatment with dendritic cells and antitransforming growth factor-β (anti-TGF-β) antibody on the elimination of regulatory T cells and the inhibition of tumor growth was investigated. The effects of the combination treatment with dendritic cells and anti-TGF-β antibody on the enhancement of systemic immune responses and inhibition of metastatic tumor growth were investigated in a murine osteosarcoma (LM8) model. To evaluate activation of the immune response, we established the following three groups of C3H mice (60 mice total): (1) excision only; (2) tumor excision and administration of anti-TGF-β antibody; and (3) tumor excision and administration of dendritic cells exposed to cryotreated tumor lysates with anti-TGF-β antibody. The mice that received dendritic cells exposed to cryotreated tumor lysates with anti-TGF-β antibody showed increased numbers of CD8(+) T lymphocytes, reduced regulatory T lymphocytes in the metastatic lesion, and inhibition of metastatic growth. The combined therapy group showed reduced numbers of regulatory T lymphocytes in the spleen and high serum interferon γ level. The control of the inhibitory condition induced by regulatory T cells is important to improve the suppression of the cytotoxic lymphocytes. Combining dendritic cells with anti-TGF-β antibody enhanced the systemic immune response. We suggest that our immunotherapy could be developed further to improve the treatment of osteosarcoma.