GENERATION OF A MONOCLONAL-ANTIBODY THAT INHIBITS THE PROCOAGULANT ACTIVITY OF VARIOUS CANCER CELL-LINES

BACKGROUND. Tumor procoagulant is one of the factors responsible for d isseminated intravascular coagulation and metastasis. The authors foun d procoagulant activity in LK52 human squamous cell carcinoma cells, w hich they designated cancer cell-derived blood coagulating activity 1 (CCA-1). A monoclonal antibody (MoAb) was generated to characterize th is CCA-1 procoagulant activity. To date, antibodies that show an inhib itory effect on procoagulant activity as well as high reactivity in ca ncer cells are well known for their tissue factor specificity. METHODS , Characterization of the procoagulant activity of CCA-1 was performed and an anti-CCA-1 MoAb, FS01, was generated. CCA-1 expression on the cancer cell surface was examined by now cytometry. Procoagulant activi ty of various cancer cell lines and the inhibitory effect of the FS01 MoAb on this procoagulant activity was monitored by a clot timer. RESU LTS, The enzymologic character differed from that of cancer procoagula nt (CP). The FS01 MoAb inhibited the procoagulant activity of CCA-1, b ut did not inhibit that of tissue factor. A positive correlation was o bserved between the expression intensity of CCA-1 and the inhibitory e ffect of the FS01 MoAb on the procoagulant activity of cancer cell lin es. Expression of CCA-I was observed more frequently than that of tiss ue factor in human cancer cell lines. CONCLUSIONS, The FS01 MoAb gener ated in the current study is a new antibody that reacts with various c ancer cell lines, but not with normal cells. FS01 inhibits cancer cell -derived procoagulant activity and does not react with tissue factor a nd CP. CCA-1, which is recognized by the FS01 MoAb, appears to play a major role in cancer cell-derived procoagulant activity. (C) 1998 Amer ican Cancer Society.