Open AccessNovel cucurmosin‐based immunotoxin targeting programmed cell death 1‐ligand 1 with high potency against human tumor in vitro and in vivo
Author(s) -
Zhang Caiyun,
Xiong Jiani,
Lan Yinxiang,
Wu Jingyu,
Wang Chengyan,
Huang Zhihong,
Lin Jizhen,
Xie Jieming
Publication year - 2020
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.14549
Subject(s) - immunotoxin , in vivo , potency , in vitro , cancer research , programmed cell death , ligand (biochemistry) , apoptosis , pharmacology , chemistry , medicine , cytotoxicity , biology , biochemistry , receptor , microbiology and biotechnology
Immunotoxins are Ab‐cytotoxin chimeric molecules with mighty cytotoxicity. Programmed cell death 1‐ligand 1 (PD‐L1), is a transmembrane protein expressed mainly in inflammatory tumor tissues and plays a pivotal role in immune escape and tumor progression. Although PD‐L1 immune checkpoint therapy has been successful in some cases, many patients have not benefited enough due to primary/secondary resistance. In order to optimize the therapeutic efficacy of anti‐PD‐L1 mAb, we used durvalumab as the payload and CUS 245C , a type I ribosome‐inactivating protein isolated from Cucurbita moschata , as the toxin moiety, to construct PD‐L1‐specific immunotoxin (named D‐CUS 245C ) through the engineered cysteine residue. In vitro, D‐CUS 245C selectively killed PD‐L1 + tumor cells. In vivo studies also showed that D‐CUS 245C had obvious antitumor effect on PD‐L1 + human xenograft tumors in nude mice. In conclusion, in the combination of the toxin with mAb, this study developed a new immunotoxin targeting PD‐L1, emphasizing a novel and promising treatment strategy and providing a valuable way to optimize cancer immunotherapy.