Monoclonal antibodies conjugation with toxins

Lambert, J.M., Senter, P.D., Yau-Young, A., Blattler, W.A., and Goldmacher, V.S. (1985) Purified immuno-toxins that are reactive with human lymphoid cells Monoclonal antibodies conjugated to the ribosomeinactivating proteins gelonin and the pokeweed antiviral proteins./. Biol. Chem. 260, 12035-12041. 

Clinically, monoclonal antibodies are also proposed as drug delivery vehicles in certain tumors where specific tumor-associated antigens are expressed. In this context, investigators have found that by conjugating toxins such as the A chain polypeptide of the plant protein ricin or the bacterial toxin from Corynebacterium diphtheriae to monoclonal antibodies specific for certain tumor type, as few as one or two molecules of antibody-toxin conjugate can destroy a tumor cell in vitro. Some success has also been obtained in clinical trials with monoclonal antibody-toxin conjugates. 

Preclinical studies should address the potential toxicity due to inappropriate release of the conjugated toxin. Preclinical toxicology of monoclonal antibodies may not require extensive animal studies but should be examined for cross-reactivity with antigenic epitopes present on normal cells in vitro and for the presence of human or rodent vimses. Early clinical trial should involve biodistribution studies with radiolabelled material. 

The method described has been used to prepare antibody-toxin conjugates containing mouse and rat monoclonal antibodies of various IgG subtypes and polyclonal antibody from several animal species. Modifications of this method have also been used to prepare conjugates with antibodies of other classes. 

For example. Immunization with T-2-HS-BSA conjugates resulted In monoclonal antibodies from different laboratories that each have different specificities. Some monoclonal antibodies have high specificity against HT-2 toxin (49), the others have specificity against 3 -OH-T-2 toxin (51). Since TCTCs have different side chains, the diversity of antibody specificity for those monoclonal antibodies might be due to the hydrolysis of either the Immunogen In the Immunization process or the hydrolysis of the T-2 toxin... 

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