Immunomodulatory activity of lenvatinib contributes to antitumor activity in the Hepa1 ‐6 hepatocellular carcinoma model

Lenvatinib is a multitargeted tyrosine kinase inhibitor that selectively inhibits VEGFR1 ‐3, FGFR1‐4, PDGFRα, RET and KIT. Here, we show that lenvatinib has immunomodulatory activity, which plays a role in the antitumor activity of single lenvatinib treatment, and enhances the antitumor activity of anti‐PD‐1 antibody in the combination treatment in the Hepa1‐6 mouse HCC synge neic tumor model. AbstractAngiogenesis inhibitors such as lenvatinib and sorafenib, and an immune checkpoint inhibitor (ICI), nivolumab, are used for anticancer therapies against advanced hepatocellular carcinoma (HCC). Combination treatments comprising angiogenesis inhibitors plus ICIs are promising options for improving clinical benefits in HCC patients, and clinical trials are ongoing. Here, we investigated the antitumor and immunomodulatory activities of lenvatinib (a multiple receptor tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor 1 ‐3, fibroblast growth factor receptor 1‐4, platelet‐derived growth factor receptor α, KIT and RET) and the combined antitumor activity of lenvatinib plus anti‐programmed cell death 1 (PD‐1) antibody in the Hepa1‐6 mouse HCC syngeneic model. We found that the antitumor activities of lenv atinib and sorafenib were not different in immunodeficient mice, but lenvatinib showed more potent antitumor activity than sorafenib in immunocompetent mice. The antitumor activity of lenvatinib was greater in immunocompetent mice t...
Source: Cancer Science - Category: Cancer & Oncology Authors: Tags: ORIGINAL ARTICLE Source Type: research