Immunotoxins containing A-chain of mistletoe lectin I are more active than immunotoxins with ricin A-chain.
Conjugates of anti-CD25 monoclonal antibodies against cell surface IL-2 receptor with MLIA and RTA were prepared and investigated. Both of the immunotoxins had high specific cytotoxic activity on target cells. The IC50 value of the anti-CD25/MLIA immunotoxin was 15-fold greater than that of the anti-CD25/RTA. Previous studies of the anti-CD5 immunotoxins with MLIA and RTA showed that the anti-CD5/MLIA IT was 80-fold more active than anti-CD5/RTA IT [Tonevitsky et al. (1991) Int. J. Immunopharmacol. 13, 1037-1041]. The surface hydrophobicity of the MLI A-chain was 4-fold higher than that of the ricin A-chain as estimated by binding with ANS. In model experiments with small unilamellar DMPC liposomes, MLIA but not RTA increased the turbidity of liposome suspensions at pH 4.5. Our results indicate that the greater cytotoxic activity of the MLI A-chain immunotoxin probably provided a higher surface hydrophobicity of the protein and the ability to interact with phospholipid membranes.
Tonevitsky
A G
AG
State Scientific Center for Genetics and Selection of Microorganisms, Moscow, Russian Federation.
Agapov
I I
II
Shamshiev
A T
AT
Temyakov
D E
DE
Pohl
P
P
Kirpichnikov
M P
MP
D000817:Anilino Naphthalenesulfonates; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D000922:Immunotoxins / Q000737:chemistry / Q000494:pharmacology*; D008563:Membrane Lipids / Q000737:chemistry; D015335:Molecular Probes; D010743:Phospholipids / Q000737:chemistry; D028321:Plant Preparations; D010940:Plant Proteins; D054790:Ribosome Inactivating Proteins, Type 2; D012276:Ricin / Q000737:chemistry*; D014118:Toxins, Biological / Q000737:chemistry*
D000817:Anilino Naphthalenesulfonates; D000922:Immunotoxins; D008563:Membrane Lipids; D015335:Molecular Probes; D010743:Phospholipids; D028321:Plant Preparations; D010940:Plant Proteins; D054790:Ribosome Inactivating Proteins, Type 2; D014118:Toxins, Biological; C009674:ribosome inactivating protein, Viscum; C027132:1-anilino-8-naphthalenesulfonate; D012276:Ricin