Gastrointestinal Carcinoma Antigen GA733: Target for Immunodestruction and Potential Modifier of Invasiveness and Chemoresponsiveness

Extract

Ligation of cell surface receptors for extracellular matrices and for other cells, including members of the integrin family of receptors, CD44, and the cadherins, generates downstream signals necessary for cellular differentiation, gene expression, the induction of ion fluxes, and the regulation of tumor progression, invasion, and metastasis (1–5). The role of altered expression of members of the integrin family and the E-cadherin family of receptors in tumor development and progression has been intensely studied during the last 10 years (6–8). The report by Basak et al. (9) appearing in this issue of the Journal focuses on the ability of a less well understood homophilic adhesion receptor, the human gastrointestinal carcinoma antigen GA733, to alter growth, invasion, and metastasis of cells of a colorectal carcinoma cell line.

In earlier studies (10–15), GA733 was shown to be a potential target for passive and active immunotherapy in patients with advanced colorectal carcinoma. In a randomized phase II clinical trial (12), 189 patients with colorectal cancer (Dukes' stage C) were assigned to receive either postoperative treatment with monoclonal antibody (MAb) 17-1A, which is directed against the GA733 antigen, or no postoperative therapy. After a median follow-up of 5 years, the overall death rate was reduced by 30%, and the rate of recurrence was reduced by 27% in patients receiving the antibody. The beneficial effect was most pronounced for patients with distant metastases at first relapse.