Biochemical, cytotoxic and pharmacokinetic properties of an immunotoxin composed of a mouse monoclonal antibody Fib75 and the ribosome‐inactivating protein α‐sarcin from Aspergillus giganteus

Abstract

An immunotoxin was synthesized by the attachment of α‐sarcin, the ribosome‐inactivating protein derived from the mould Aspergillus giganteus, to a monoclonal mouse IgG2a antibody Fib75. The α‐sarcin immunotoxin exerted toxic effects in tissue culture against the EJ human bladder carcinoma cell line, expressing the antigen recognised by the Fib75 antibody, inhibiting the incorporation of [3H]leucine by 50% at a concentration of 0.46 nM. The cytotoxic effects of the α‐sarcin immunotoxin were indistinguishable from those of a Fib75 immunotoxin made with ricin A chain. Fib75‐α‐sarcin was cleared from the circulation of the rat with biphasic kinetics following intravenous administration. The α‐ and β‐phase half‐lives were 0.8 h and 6 h, respectively, similar to the serum half‐lives of analogous Fib75 immunotoxins made with ribosome‐inactivating proteins derived from plants. α‐Sarcin was completely stable in physiological saline buffer at 37°C, whereas the ribosome‐inactivating activity of ricin A chain was gradually lost under identical conditions. α‐Sarcin may be a valuable alternative to ricin A chain for the construction of therapeutic immunotoxins because of its smaller size and greater thermostability. Copyright © 1991, Wiley Blackwell. All rights reserved