Systemic blockade of transforming growth factor-beta signaling augments the efficacy of immunogene therapy.

ABSTRACT: Locally produced transforming growth factor-beta (TGF-beta) promotes tumor-induced immunosuppression and contributes to resistance to immunotherapy. This article explores the potential for increased efficacy when combining immunotherapies with TGF-beta suppression using the TGF-beta type I receptor kinase inhibitor SM16. Adenovirus expressing IFN-beta (Ad.IFN-beta) was injected intratumorally once in established s.c. AB12 (mesothelioma) and LKR (lung cancer) tumors or intratracheally in a Kras orthotopic lung tumor model. Mice bearing TC1 (lung cancer) tumors were vaccinated with two injections of adenovirus expressing human papillomavirus-E7 (HPV-E7; Ad.E7). SM16 was administered orally in formulated chow. Tumor growth was assessed and cytokine expression and cell populations were measure

SUBMITTER: Kim S 

PROVIDER: S-EPMC2637471 | biostudies-literature | 2008 Dec

REPOSITORIES: biostudies-literature