Journal
INTERNATIONAL IMMUNOPHARMACOLOGY
Volume 110, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.intimp.2022.109076
Keywords
Apoptosis; Cancer; Cytotoxicity; Immunotoxin; Stx2a
Categories
Funding
- Tehran University of Medical Sciences & Health Services [29903-27- 03-94]
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Immunotoxins, a type of targeted therapy, can kill cells using highly potent bacterial, fungal or plant toxins. In this study, a Stx-based immunotoxin was designed and used to selectively induce cytotoxicity and apoptosis in Fn-14-positive cells related to colon and lung cancer.
Immunotoxins are regarded as a type of targeted therapy for killing cells by highly potent bacterial, fungal or plant toxins. Shiga like toxins (SLTs) are a group of bacterial AB5 protein toxins that inhibit host cell protein synthesis through the removal of a single adenine residue from the 28S rRNA and lead to apoptosis. Here, we described the design and usage of a Stx-based immunotoxin that can induce the selective cytotoxicity and apoptosis in Fn-14-positive cells related to the colon and lung cancer. In the present study, the Stx2a-PE15-P4A8 fusion protein was expressed efficiently in E. coli (DE3) system when driven from inclusion bodies by 8 M urea. The Stx2a-PE15-P4A8 fusion protein was expressed efficiently in E. coli (DE3) system and then purified. The purified fusion protein could specifically target Fn-14 receptor existed on colon and lung cancer cell lines and suppress these cells in a dose-dependent manner. In addition, the protein was able to nearly 50 % of apoptotic cell death and maintains about 54 % of its stability after 24 h of incubation in mouse serum at 37 C. Compared to PE38-P4A8 construct in our previous study, these results showed that the Stx2a-PE15-P4A8 construct can be an efficient therapeutic candidate for cancer immunotherapy.
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