Abstract 3254: A novel TGFβRI inhibitor suppresses tumor progression by increasing T-cell infiltration into tumor

TGF-beta (TGF-β) pathways, despite serving as tumor suppressor in early stage of carcinogenesis, have shown to be one of the key tumor-promoting factors in later-stage tumor progression. TGF-β receptor type 1 (TGFβRI) inhibitors have shown great potentials in their anti-tumor and anti-metastasis efficacy in preclinical studies and some of them are being tested in the clinical settings. A specific TGFβRI inhibitor YL-13027 was developed at Yingli Pharmaceutical. Our previous data have shown that YL-13027 significantly inhibited the T cell differentiation into Treg and the secretion of IL-10 in vitro, as well as tumor growth in immune-competent mice with CT26 tumors. Our further studies indicated that the anti-tumor efficacy of YL-13027 was largely mediated by T cells. More importantly, YL-13027 synergistically enhanced the anti-tumor efficacy of anti-PD-L1 antibody in CT26 model. YL-13027 displayed significant anti-tumor efficacy in other syngeneic mouse tumor models tested including orthotopic murine breast carcinoma 4T1 model in BALB/c mice and murine hepatocellular carcinoma Hepa1-6 model in C57BL/6 mice. YL-13027 is well tolerated by the animals with no treatment-related toxicity observed in these efficacy studies. Analyses of tumors treated with YL-13027 revealed that YL-13027 significantly increased the number of tumor-infiltrating lymphocytes in tumors. These data suggest that YL-13027, a novel TGFβRI inhibitor, represents a promising and safe immune modulator and shows great potential as a cancer immuno-therapeutics. Citation Format: Xu Zusheng, Yangtong Lou, Qiang Zhao, Wei Wang. A novel TGFβRI inhibitor suppresses tumor progression by increasing T-cell infiltration into tumor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3254.