8 



specificity in the uptake of conjugates. Cytosine ara- 

 binoside-albumin conjugates were effective in inhibiting 

 viral replication within mouse liver cells, suggesting 

 retention of toxicity after conjugation. However, the high 

 molecular weight complexes that resulted from the synthesis, 

 make non-specific endocytosis a likely route for uptake of 

 these conjugates (Balboni et al., 1976). Greater specificity 

 of uptake and apparent toxicity was obtained with conjugates 

 of p-phenylenediamine mustard and anti-lymphoid cell anti- 

 bodies (Davies and O'Neil, 1977). Other conjugates of 

 chlorambucil and antibodies against specific cell types 

 displayed selective toxicity and some degree of chemothera- 

 peutic potential, in vivo (Ghose et al . , 1972). Anti- 

 Ehrlich ascites tumor cell antibody-chlorambucil conjugates 

 also were effective in treatment of the neoplasia (Flechner, 

 1973). However, in similar studies, Rubens and Dulbecco 

 (1974) have demonstrated a lack of covalent association of 

 chlorambucil with the antibodies, making it difficult to 

 ascertain the exact mechanism of the observed toxicity. 



Perhaps the most effective conjugates of immunoglo- 

 bulin and inhibitors that interact with DNA have been 

 conjugates of daunomycin and anti-mouse lymphoid cell 

 tumor antibodies (Levy et al., 1975). These conjugates 

 were examined for both inhibition of specific tumor cell 

 growth .in vivo and for i_n vitro inhibition of tumor cell 

 RNA synthesis. In comparison to daunomycin linked to 

 non-specific immunoglobulin, the anti-tumor antibody-daunomycin 



