Targeted Stimulation of Dendritic Cells via MDK-ALK -STAT3 Inhibition by Dendritic Cell-derived Exosomes

¹ School of Pharmacy, China Pharmaceutical University, Nanjing, 211198, China
² School of Clinical Medicine, Bengbu Medical University, Bengbu, 233030, China
³ School of Life Science, Wuhan University, Wuhan, 430000, China
⁴ School of Basic Medical Sciences, Xi’an Jiaotong University, Xi’an, 710049, China

^* Corresponding author: This email address is being protected from spambots. You need JavaScript enabled to view it.

Abstract

Lung cancer remains to be one of the deadliest cancer worldwide. Among its multiple phenotypes, ALK-mutated lung adenocarcinoma (LUAD) is well-known for its resistance to immunotherapy, while resistance to targeted therapy will eventually develop due to further mutations, calling for novel treatment strategies. In this article, we propose the hypothesis that its resistance to immunotherapy may be due to impaired dendritic cell functions, affected by the recently discovered MDK-ALK-STAT3 axis. In light of this, we propose to design a dendritic cell-derived exosome under the stimulation of tumor antigens, carrying Ceritinib into DCs rather than tumor cells. Potentially, this targeting strategy will block the MDK-ALK-STAT3 axis and stimulate dendritic cell function, while circumventing targeted therapy resistance, resulting in anti-tumor immunity and addressing the problem of immunotherapy ineffectiveness, providing novel therapeutic methods for ALK-mutated LUAD patients.