10 



transformed cells (Moolten et al, 1976). IleLa cells that 

 had been coated with hapten (2 , 4 , 6-trinitrophenyl sulfuric 

 acid) were killed by diphtheria toxin-antibody conjugate 

 only when the antibody was hapten specific (Philpott et al., 

 1973) . Mouse anti-lactate dehydrogenase antibody when 

 coupled to diphtheria toxin resulted in a conjugate more 

 toxic for Erhlich ascites cells than for normal mouse 

 kidney cells due to increased expression of lactate dehy- 

 drogenase on the ascites cells (Samagh and Gregory, 1972) . 

 Thorpi et al. (1978) coupled purified antilymphocytic 

 globulin-chlorambucil conjugates to dephtheria toxin via 

 an activated anhydride reaction that yielded well defined 

 conjugates which could readily be purified by gel filtration. 

 The conjugates were significantly more toxic to cultured 

 lymphoblastoid cells than was the free toxin. The con- 

 jugates overcame a significant problem with the synthesis 

 of diphtheria toxin-protein conjugates described above. 

 Dephtheria toxin is a protein macromolecule which is readily 

 cross-linked during most of the procedures used to produce 

 conjugates. This results in ill-defined preparations of 

 varying compositions and specificities. 



The advantage to using dephtheria toxin resides in its 

 mechanism of toxicity. Diphtheria toxin is a potent inhi- 

 bitor of eucaryotic protein synthesis by virtue of its 

 catalytic ADP-ribosylation of elongation factor, EF-2 

 (Collier, 1975) . 



