THE EFFECT OF CIRCULATING ANTIGEN ON THE BIODISTRIBUTION OF THE ENGINEERED HUMAN-ANTIBODY HCTM01 IN A NUDE-MICE MODEL

Clinical studies are currently underway to assess the biodistribution and therapeutic potential of the genetically engineered human antibody hCTM01 directed against polymorphic epithelial mucin (PEM) in patient s with ovarian carcinoma. The present study was undertaken to assess t he effect of circulating PEM antigen on the biodistribution of the ant i-PEM antibody in mice bearing MUC-1 transfected adenocarcinoma cell l ines. Tumour xenografts were established from three cell lines: 413-BC R, which expressed antigen on the cell surface and also shed antigen i nto the circulation, E3P23, which expressed the antigen but did not sh ed into the circulation, and a negative control (410.4 MUCI). Groups o f five mice were injected with 1.0 mg/kg antibody, imaged after 72 h a nd then sacrificed, followed by assay of tissue uptake. The results sh owed a clear difference in the tumour and liver uptake, with the non-s ecreting cell line showing almost twice the tumour uptake and approxim ately 20% of the liver uptake of the secreting cell line.