A HUMAN NATURAL ANTIBODY TO ADENOCARCINOMA THAT INHIBITS TUMOR-CELL MIGRATION

We characterized a natural human antibody to adenocarcinomas and inves tigated the biological role of this Ab/Ag complex in cancer expansion. Human monoclonal antibodies (HuMAbs) were generated with hybridoma fu sion methods using regional nodal lymphocytes of colon carcinoma patie nts. Among 1036 HuMAbs, only one, termed SK1, an IgM, was adenocarcino ma specific in the immunohistochemical study. The antigen recognized b y SKI (Ag-SK1) was a glycoprotein with a molecular weight of 42-46 kDa . The expression of AS-SKI on carcinoma cells varied according to the cell growth periods but was independent of cell cycle state as elucida ted by two-colour fluorescence-activated cell sorter (FACS) analysis. A dot-blot analysis showed that the concentration of AS-SKI per total protein differed considerably among eight colon carcinoma cells examin ed and that the difference was closely correlated with the invasion ca pacity of the cells as assessed by a microchemotaxis assay. Furthermor e, up to 87% of cell migration was inhibited by SK1 in a dose-dependen t manner. These data suggested that AS-SK1 is metabolized and expresse d on highly invasive carcinoma cells. In addition, it appears that, al though rare, some patients do mount an anti-cancer antigen response in their draining lymph nodes. A HuMAb such as SK1 may be a good candida te for the treatment of cancer invasion and metastasis.