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 CUS245C, a type I ribosome-inactivating protein isolated from Cucurbita moschata, as the toxin moiety, to construct PD-L1-specific immunotoxin (named D-CUS245C) through the engineered cysteine residue. In vitro, D-CUS245C selectively killed PD-L1+ tumor cells. In vivo studies also showed that D-CUS245C 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.
Bibliographical noteFunding Information:
We thanks Dr Liqun Luo for help with the experiment. This research was funded by the National Science Foundation of China (No. 30772587), the Natural Science Foundation of Fujian Province (No. 2016J01769), the Fujian Province health and family planning scientific research talent training project (No. 2018‐CX‐40), and Startup Fund for scientific research, Fujian Medical University (No. 2019QH1196).
© 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.
- targeted therapy