Potentiation of cytotoxic activity of immunotoxins on cultured human cells.
The cytotoxic activity against human tumor cells of toxic conjugates of Pseudomonas exotoxin with anti-transferrin receptor antibody or epidermal growth factor was potentiated up to 10 to 20-fold by the calcium antagonists verapamil, D-600, and diltiazem and by the lysosomotropic agent beta-glycylphenyl-naphthylamide. The potentiating activity of these agents could be predicted by measuring the inhibition of protein synthesis by the immunotoxins on various cell lines. The use of potentiating agents such as these in combination with immunotoxins may prove useful in the treatment of some human cancers.
Akiyama
S
S
Seth
P
P
Pirker
R
R
FitzGerald
D
D
Gottesman
M M
MM
Pastan
I
I
D000912:Antibodies, Neoplasm / Q000008:administration & dosage / Q000276:immunology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003603:Cytotoxins / Q000008:administration & dosage / Q000494:pharmacology*; D004151:Dipeptides / Q000494:pharmacology*; D004357:Drug Synergism; D004815:Epidermal Growth Factor / Q000276:immunology; D006801:Humans; D009363:Neoplasm Proteins / Q000096:biosynthesis; D009369:Neoplasms / Q000188:drug therapy; D011956:Receptors, Cell Surface / Q000276:immunology; D011990:Receptors, Transferrin
D000912:Antibodies, Neoplasm; D002121:Calcium Channel Blockers; D003603:Cytotoxins; D004151:Dipeptides; D009363:Neoplasm Proteins; D011956:Receptors, Cell Surface; D011990:Receptors, Transferrin; C041865:glycylphenylalanine 2-naphthylamide; D004815:Epidermal Growth Factor