Incorporation of SKI-G-801, a Novel AXL Inhibitor, With Anti-PD-1 Plus Chemotherapy Improves Anti-Tumor Activity and Survival by Enhancing T Cell Immunity

• DOI: 10.3389/fonc.2022.821391
• Publication Date: 2022-03-09T10:14:31Z
• Authors: Wongeun Lee; Dong Kwon Kim; Chun-Bong Synn; Hee Kyu Lee; Sungho Park; Dong-Sik Jung; Yewon Choi; Jae Hwan Kim; Youngseon Byeon; Young Seob Kim; Seul Lee; Soyeon Lee; Yunjoo Joo; Eun Ji Lee; Mi Ran Yun; Seong Gu Heo; Wookyeom Yang; Ji Eun Jung; Eun Kyung Kim; Jooyeon Park; June Dong Park; Doo Jae Lee; Hyeon-Woo Kim; Sun Min Lim; Min Hee Hong; Beung-Chul Ahn; Jii Bum Lee; Kyoung-Ho Pyo
• Keywords: Pemetrexed; Immune checkpoint

A recently developed treatment strategy for lung cancer that combines immune checkpoint inhibitors with chemotherapy has been applied as a standard adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC), it improved the outcomes of chemotherapy. Maintenance anti-PD-1 antibody (aPD-1) enhances effect immunochemical combination therapy improves therapeutic efficacy, which contributes toward significant improvement in patient survival rates. The AXL receptor tyrosine kinase (AXL), is expressed tumor cells, plays an essential role resistance cancers to immunotherapy, stimulates signaling associated epithelial-mesenchymal transition (EMT) metastatic cancer. thus attractive target controlling anti-tumor therapies. In this study, we examined on activation growth TC1 C3PQ mouse models, context clinical immunotherapy/chemotherapy maintenance treatment, using aPD-1 with/without pemetrexed. To determine optimal timing administration SKI-G-801, inhibitor, investigated its effects based inclusion at immunochemotherapy stages. We also performed flow cytometry-based profiling myeloid cells lymphoid different points schedule, investigate inhibitor. addition SKI-G-801 inhibitor stage, well produced best results, inhibition was observed both models. Both models exhibited increased proportion effector memory helper T expression CD86+ macrophages. Especially, regulatory were significantly reduced model there increase central cytotoxic infiltration macrophages high CD80 model. These results suggest consistent previous studies inhibitors. It expected from study will serve stepping stone research improve existing care.