1q24.1

Colorectal cancer

Colorectal cancer marker.
Although the biochemical, immunological and molecular biology of the A33 antigen has been extensively characterized, the function of the molecule remains unknown. The antigen has several identified properties that contribute to a potential therapeutic target for colon cancer. The A33 antigen is expressed homogenously and at high levels in colorectal carcinomas, there are a high number of A33 binding sites per cell and it is not shed or secreted into the blood stream (Welt et al., 1990). In addition, upon mAB binding to the A33 antigen, the antibody-antigen complex is internalized and sequestered in vesicles (Daghighian et al., 1996).
Selective immunological targeting of tumors with monoclonal antibodies (mAb) is an important therapeutic approach in cancer therapy. Clinical imaging and biopsy-based biodistribution studies using radiolabeled murine mAb A33 demonstrated specific targeting to antigen-positive tumor tissues in 95% of colorectal patients with tumor retention for up to six weeks (Welt et al., 1990; Welt et al., 1994). The only normal tissue reported to accumulate the radioisotope was the bowel, with clearance from the normal gastrointestinal tract within one week. Phase I and II therapy trials using ¹²⁵I- and ¹³¹I-labeled murine A33 mAb were shown to have antitumor effects without bowel toxicity, however human anti-mouse antibody development in all patients prevented repeated dosing and led to the development of humanized mAb A33 (huA33). Phase I clinical trials using multiple dose schedules of ¹²⁵I- and ¹³¹I-labled huA33 mAb in patients with colorectal carcinoma have been conducted and have shown safety and possible efficacy, with future trials proposed (Chong et al., 2005; Scott et al., 2005).