Improved detection of the early stages of colon cancer by determining both free circulating and immune complex-bound antigens reactive with monoclonal antibody

The measurement of both immune complex-bound and free unbound tumor-associated antigen was evaluated independently on a panel of sera from colon cancer patients by radioimmunoassay (RIA). A monoclonal antibody (mAb 46.3) raised against secreted antigens from human colon cancer cells in vitro was utilized in the RIA. When circulating immune complexes alone were analyzed, the data demonstrated that 5 of 5 (100%) Dukes' A patients and 11 of 16 (69%) Dukes' B patients had elevated levels of immune complexes reactive with mAb 46.3. Analysis of free circulating antigens demonstrated elevated levels of mAb 46.3-reactive antigen present in 5 of 5 (100%) Dukes' A patients and 15 of 16 (95%) Dukes' B patients. However, by analyzing total reactivity, defined by combining results from RIA with free and immune complex-bound antigen, the sensitivity of detection for Dukes' B increased to 16 of 16 (100%). Total antigen levels in sera from patients with benign diseases (ulcerative colitis, Crohn's disease, adenoma) were not significantly different from normal controls. Analysis of both free and bound antigen in RIA is, therefore, a more sensitive indicator than RIA with immune complex alone. For the advanced stages of disease, only 1 of 5 (20%) Dukes' C and 0 of 5 (0%) Dukes' D sera were positive for reactive immune complexes. When the combined RIA was evaluated, 3 of 5 (60%) and 1 of 5 (20%) Dukes' C and D sera, respectively, were positive with mAb 46.3. Taken together, these results show that RIA with mAb 46.3 is a sensitive indicator for the early stages of colon cancer.