ANTITUMOR RIBONUCLEASE, COMBINED WITH OR CONJUGATED TO MONOCLONAL-ANTIBODY MRK16, OVERCOMES MULTIDRUG-RESISTANCE TO VINCRISTINE IN-VITRO AND IN-VIVO

Onconase, a ribonuclease isolated from Rana pipiens oocytes and early embryos, is a member of the RNase A superfamily. Onconase has anti-neo plastic properties both in vitro and in vivo, and is undergoing clinic al evaluation. In the present study, Onconase was combined with or con jugated to MRK16, an anti-P-glycoprotein (Pgp) monoclonal antibody. Th e interaction of these combinations with vincristine (VCR) against par ental and multidrug resistant (MDR), Pgp expressing, human colon carci noma cells caused increased VCR cytotoxicity in vitro and enhanced sur vival of athymic nude mice given transplants of drug resistant HT-29(m dr1) cells in vivo. The results suggest that combination treatment wit h Onconase and other agents that modulate the chemosensitivity of Pgp- expressing human tumor cells has the potential to overcome MDR.