IN-VIVO EFFICACY OF NEOCARZINOSTATIN COUPLED WITH FAB HUMAN MOUSE CHIMERIC MONOCLONAL-ANTIBODY A7 AGAINST HUMAN COLORECTAL-CANCER/

The anticancer polypeptide neocarzinostatin (NCS) was covalently coupl ed to a human/mouse chimeric Fab A7 monoclonal antibody (chFabA7) and the in vivo efficacy of this conjugate was examined, NCS concentration assay was carried out, and acute toxicity and tumoricidal effects wer e examined. The concentration assay, using anti-NCS monoclonal antibod y, revealed that administration of the chA7Fab conjugate leads to a gr eater blood retention and a higher tumor accumulation of NCS, when com pared to free NCS administration. The tumoricidal effect of chA7Fab-NC S was higher than that of either free NCS or the saline control, again st antigen-positive tumors. In antigen-negative tumors there was no di fference in toxic effect among the three preparations. Values of LD(50 ), reflecting acute toxicity, were 5050 U/kg and 3600 U/kg for the chA 7Fab-NCS and the free NCS, respectively. These results suggest that ch FahA7-NCS may be a promising tool for targeting cancer chemotherapy.