We have selected the D3 MoAb/Line 10 tumor system as a model for drug/toxin-MoAb solid tumor therapy. The similarity in the immune responses of guinea pigs and man, especially with regard to anaphylactic reactions, makes the guinea pig Line 10 tumor an especially appropriate model. We have produced and characterized the D3 MoAb and it appears to display adequate levels of "tumor specificity," both in vitro and in vivo. In addition, D3 is only slightly cytotoxic, allowing good assessment of the antitumor cytotoxicity of drug/toxin conjugates. D3 is currently in bulk production and has been sent to collaborators for drug/toxin conjugation and has been radiolabelled. In vitro assessment of the amount of drug/toxin per antibody molecule and in vitro cytotoxicity and specificity studies are underway. Both diphtheria toxin A chain and doxorubicin-conjugated D3 are specifically cytotoxic for L10 cells in vitro. Diphtheria A chain-conjugated D3 has shown striking effectiveness against established L10 tumors in vivo, with no observed side effects to date. In vivo radioimaging studies are in progress, with specific tumor imaging already demonstrated. By testing various coupling procedures and drugs/toxins, we hope to identify the procedures most likely to prove successful in other in vivo tumor systems, including in man.
NIH ExPorter
NIH ExPorter