A recombinant, membrane-acting immunotoxin.
The anti-Tac antibody is known to bind to the p55 chain of the human interleukin 2 receptor. An immunotoxin was produced by genetically linking Clostridium perfringens phospholipase C (PLC) to the Fab domain of anti-Tac. For this purpose, the PLC gene, with its own promoter and signal sequence, was fused to the 5' end of the VHCH1 segment of the anti-Tac heavy chain gene. The anti-Tac light chain gene, with an attached bacterial signal sequence, was made part of the same transcriptional unit. Escherichia coli transformed with the construct secreted a recombinant immunotoxin, anti-Tac(Fab)-PLC, in an active form. Anti-Tac(Fab)-PLC bound to cells expressing the interleukin 2 receptor and inhibited protein synthesis, with a 50% inhibitory concentration of 0.02 nM (1.8 ng/ml).
Chovnick
A
A
Protein Design Labs, Mountain View, California 94043.
Schneider
W P
WP
Tso
J Y
JY
Queen
C
C
Chang
C N
CN
D000595:Amino Acid Sequence; D001483:Base Sequence; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003016:Clostridium perfringens / Q000201:enzymology / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000235:genetics* / Q000378:metabolism; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000378:metabolism; D000922:Immunotoxins / Q000378:metabolism* / Q000494:pharmacology; D008969:Molecular Sequence Data; D010957:Plasmids; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D015183:Restriction Mapping; D013601:T-Lymphocytes / Q000276:immunology; D010738:Type C Phospholipases / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology
D007140:Immunoglobulin Fab Fragments; D007143:Immunoglobulin Heavy Chains; D000922:Immunotoxins; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D010738:Type C Phospholipases