Antitumor activity in mice of an immunotoxin made with anti-transferrin receptor and a recombinant form of Pseudomonas exotoxin.
LysPE40 is a modified form of Pseudomonas exotoxin that lacks the cell-binding domain and has a chemically reactive lysine residue near the amino terminus. LysPE40 is made in Escherichia coli and secreted into the medium from which it is readily purified. Two immunotoxins were constructed by coupling LysPE40 to an antibody to the human transferrin receptor (TFR) or to an antibody to the human interleukin-2 receptor. These immunotoxins were selectively cytotoxic to receptor-bearing cells in tissue culture. Anti-TFR-LysPE40 given intraperitoneally to mice appeared rapidly in the blood and caused regression of A431 tumors growing as subcutaneous xenografts. These results show that it is possible to cause regression of a solid carcinoma by an immunotoxin if proper targeting can be achieved.
Batra
J K
JK
Laboratory of Molecular Biology, National Cancer Institute, Bethesda, MD 20892.
Jinno
Y
Y
Chaudhary
V K
VK
Kondo
T
T
Willingham
M C
MC
FitzGerald
D J
DJ
Pastan
I
I
D036002:ADP Ribose Transferases; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D001427:Bacterial Toxins; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000628:therapy*; D002460:Cell Line; D005098:Exotoxins / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D000922:Immunotoxins / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000096:biosynthesis; D009368:Neoplasm Transplantation; D011500:Protein Synthesis Inhibitors; D011550:Pseudomonas aeruginosa; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D011990:Receptors, Transferrin / Q000276:immunology*; D011994:Recombinant Proteins / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use; D014183:Transplantation, Heterologous; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A
D036002:ADP Ribose Transferases; D000911:Antibodies, Monoclonal; D001427:Bacterial Toxins; D005098:Exotoxins; D000922:Immunotoxins; D009363:Neoplasm Proteins; D011500:Protein Synthesis Inhibitors; D015375:Receptors, Interleukin-2; D011990:Receptors, Transferrin; D011994:Recombinant Proteins; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A