Pilot study using a humanized CC49 monoclonal antibody (HuCC49DeltaCH2) to localize recurrent colorectal carcinoma

CC49 is a monoclonal antibody directed against a pancarcinoma antigen (TAG-72) expressed by colorectal cancers. The use of murine CC49 in radioimmunoguided surgery (RIGS) was problematic because of the human anti-mouse antibodies (HAMA) generated. This study was designed to assess the clearance, safety, and effectiveness of localization of a complimentarity determining region (CDR)-grafted humanized domain-deleted antitumor CC49 antibody (HuCC49DeltaCH2).

After thyroid blockade, 1 mg of HuCC49DeltaCH2 radiolabeled with 2 mCi of iodine-125 was administered. All patients subsequently underwent traditional exploration followed by a survey with the gamma-detecting probe. In five patients, exploration was performed 10 to 24 days after injection, when precordial counts were sufficiently low (<30 counts per 2 seconds [cp2s]). Traditionally suggestive and probe-positive tissue was biopsied or excised and examined for the presence of carcinoma, when considered appropriate by the operating surgeon. Serum was assessed for HAMA.

Seventeen sites were identified as suggestive of carcinoma on traditional exploration and 21 by RIGS. Of these, pathologic correlation was obtained in 15. The sensitivity of RIGS was 92%, and the positive predictive value was 100%. None of the patients expressed significant HAMA.

This initial study indicates that the HuCC49DeltaCH2 monoclonal antibody, when used with RIGS, is safe and sensitive in detecting recurrent intra-abdominal colon cancer.