Fusion protein of interleukin 4 and diphtherial toxin with high cytotoxicity to cancer cells.
Receptor of human interleukin 4 (hIL4R) has been found to be present on many types of cancer, so it may be a good target for cancer therapy. Here, fusion toxin gene DT4H has been constructed by fusing DNA sequence encoding the first 389 amino acids of diphtherial toxin (DT), which can not bind its own receptor, to human interleukin 4 (hIL4) gene. In order to improve the affinity of fusion toxin for hIL4R, a circularly permuted form of hIL4 (cpIL4) was used. The fusion gene was expressed in Escherichia coli where the fusion toxin DT4H was highly expressed. Purified DT4H was very cytotoxic to cancer cell line U251 cells, and moderate cytotoxic to HepG2 and MCF-7 cells. SGC-7901 cells were insensitive to it. The cytotoxic action of DT4H was specific because it was blocked by excess hIL4. These results suggest that DT4H may be a useful agent in the treatment of certain malignancies.
Zhang
Yu-Jian
YJ
Research Center of Biotechnology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai 200233, China.
Hu
Xiao-Bo
XB
Li
Su-Xia
SX
Tian
Li-Ping
LP
Yang
Sheng-Li
SL
Gong
Yi
Y
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002460:Cell Line; D045744:Cell Line, Tumor; D003001:Cloning, Molecular; D003603:Cytotoxins / Q000737:chemistry; D004167:Diphtheria Toxin / Q000737:chemistry* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D004926:Escherichia coli / Q000378:metabolism; D006801:Humans; D015847:Interleukin-4 / Q000737:chemistry* / Q000627:therapeutic use; D007700:Kinetics; D008957:Models, Genetic; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D010957:Plasmids / Q000378:metabolism; D017434:Protein Structure, Tertiary; D019948:Receptors, Interleukin-4 / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry* / Q000378:metabolism
D000970:Antineoplastic Agents; D003603:Cytotoxins; D004167:Diphtheria Toxin; D019948:Receptors, Interleukin-4; D011993:Recombinant Fusion Proteins; D015847:Interleukin-4