CD47 blockade improves the therapeutic effect of osimertinib in non-small cell lung cancer.
10.1007/s11684-022-0934-1
- Author:
Wei-Bang YU
1
;
Yu-Chi CHEN
1
;
Can-Yu HUANG
1
;
Zi-Han YE
1
;
Wei SHI
1
;
Hong ZHU
2
;
Jia-Jie SHI
1
;
Jun CHEN
3
;
Jin-Jian LU
4
Author Information
1. State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, 999078, China.
2. Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, and Cancer Center of Zhejiang University, Zhejiang University, Hangzhou, 310000, China.
3. Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510000, China.
4. State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, 999078, China. jinjianlu@um.edu.mo.
- Publication Type:Journal Article
- Keywords:
ADCP;
EGFR;
anti-CD47 antibody;
combination strategy;
osimertinib
- MeSH:
Humans;
Mice;
Animals;
Carcinoma, Non-Small-Cell Lung/metabolism*;
Lung Neoplasms/metabolism*;
Acrylamides/pharmacology*;
ErbB Receptors/metabolism*;
Cell Line, Tumor;
CD47 Antigen/therapeutic use*
- From:
Frontiers of Medicine
2023;17(1):105-118
- CountryChina
- Language:English
-
Abstract:
The third-generation epidermal growth factor receptor (EGFR) inhibitor osimertinib (OSI) has been approved as the first-line treatment for EGFR-mutant non-small cell lung cancer (NSCLC). This study aims to explore a rational combination strategy for enhancing the OSI efficacy. In this study, OSI induced higher CD47 expression, an important anti-phagocytic immune checkpoint, via the NF-κB pathway in EGFR-mutant NSCLC HCC827 and NCI-H1975 cells. The combination treatment of OSI and the anti-CD47 antibody exhibited dramatically increasing phagocytosis in HCC827 and NCI-H1975 cells, which highly relied on the antibody-dependent cellular phagocytosis effect. Consistently, the enhanced phagocytosis index from combination treatment was reversed in CD47 knockout HCC827 cells. Meanwhile, combining the anti-CD47 antibody significantly augmented the anticancer effect of OSI in HCC827 xenograft mice model. Notably, OSI induced the surface exposure of "eat me" signal calreticulin and reduced the expression of immune-inhibitory receptor PD-L1 in cancer cells, which might contribute to the increased phagocytosis on cancer cells pretreated with OSI. In summary, these findings suggest the multidimensional regulation by OSI and encourage the further exploration of combining anti-CD47 antibody with OSI as a new strategy to enhance the anticancer efficacy in EGFR-mutant NSCLC with CD47 activation induced by OSI.
