Reversal of intracellular toxicity of the trichothecene mycotoxin T-2 with monoclonal antibody.

The trichothecene mycotoxin T-2 is a potent inhibitor of intracellular protein synthesis. We have previously shown that a mouse immunoglobulin G1 monoclonal antibody (15H6) specific for T-2 toxin can neutralize the in vitro protein synthesis inhibitory effect of the toxin in human B-lymphoblastoid cultures, and protect rats from lethal toxemia. We now report that these monoclonal antibodies can induce the net efflux of [3H]-T-2 toxin from poisoned human B-lymphoblastoid cells in vitro, and restore protein synthesis. Administration of the monoclonal antibodies (250 mg/kg) 30 min before infusion of a lethal dose (1 mg/kg) of T-2 toxin causes the sequestration of the toxin in the plasma compartment. When administered 35 min after T-2 toxin, a time when the bulk of toxin is in the tissues, the monoclonal antibodies facilitate the migration of toxin back into the plasma compartment. These data demonstrate that monoclonal antibodies can be of therapeutic value against an intracellular toxin.

Monoclonal antibodies to T-2 toxin. In vitro neutralization of protein synthesis inhibition and protection of rats against lethal toxemia.

A murine monoclonal antibody (15H6) against the trichothecene mycotoxin T-2 was capable of neutralizing the in vitro protein synthesis inhibitory effect of T-2 toxin in human B lymphoblastoid cultures. It was further shown that 15H6 given to rats (250 mg/kg) 30 min before or 15 min after a lethal dose (1 mg/kg) of T-2 toxin conferred 100% survival. A lower dose of 15H6 (125 mg/kg), given 15 min after the lethal dose of T-2 toxin, protected 25% of the rats. An increased time to death and 45% survival was seen in rats given the full dose of 15H6 antibody 60 min after lethal toxin. These data are the first demonstration of effective prophylaxis and therapy for T-2 toxemia.