Cytotoxic effect of ricin A-chain conjugates containing monoclonal antibodies against human erythroid cells.
Selective elimination of human erythroblastoid cells by the conjugate of the A-chain of a plant toxin ricin (RA) and monoclonal antibody (MAb) HAE9 (IgM) directed against human erythroblast antigen (Ag-Eb) has been demonstrated. In comparative experiments, MAb HAE3 (IgM) against human glycophorin-A was used. On average, the conjugates obtained contained two A-chain molecules and one antibody molecule. Efficiency of cytotoxic action of native ricin and conjugates was compared both with the amount of binding sites on the surface of K562 cells and the internalization rate of these proteins. The association constants of the proteins proved to be almost the same (ka = 10(8) M-1). The ID50 values were 1.1 x 10(-11), 3.2 x 10(-10) and 3.1 x 10(-9) M for ricin, HAE9/RA and HAE3/RA, respectively. Ammonium chloride at a concentration of 10 mM increases the cytotoxic effect of the HAE9/RA conjugate approximately 10 times and does not change the activity of the HAE3/RA conjugate.
Tonevitsky
A G
AG
Institute for Genetics and Selection of Industrial Microorganisms, Moscow, Russia.
Agapov
I I
II
Ershova
G V
GV
Sarma
T
T
Toptygin AYu
Mechetner
E B
EB
D000911:Antibodies, Monoclonal / Q000378:metabolism; D001665:Binding Sites; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D004900:Erythroblasts / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D000922:Immunotoxins / Q000378:metabolism / Q000494:pharmacology*; D012276:Ricin / Q000378:metabolism / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D000922:Immunotoxins; D012276:Ricin