Human monoclonal antibody against a tissue polypeptide antigen-related protein from a patient with a signet-ring cell carcinoma of the stomach.

For a comparative study of the humoral immunity of patients with gastric signet-ring cell carcinoma, lymphocytes from spleen and lymph nodes were fused with the heteromyeloma SPM4-0. Immunoglobulin-producing clones were primarily tested in binding assays on autologous and allogeneic tumor cells and tissues. One of the resulting human monoclonal antibodies, designated 56/16 (IgM, lambda), was found to be suitable for a detailed biochemical characterization. Immunoblotting and comparative two-dimensional gel electrophoresis on cell and tissue extracts as well as on preparations of the cytoskeleton revealed that the main epitope is not an integral membrane molecule but a degradation product of cytokeratin 8, which is a main component of the tumor marker, tissue polypeptide antigen. The Mr 38,000/45,000 antigen could be identified in tumor and normal tissues, with highest expression in secretory cells and organs. Thus, the human monoclonal antibody 56/16 might represent an immune response in the patient against breakdown products of cytokeratin 8, which are released from the tumor cells during cell division, secretion, or cell death. A possible association of the antibody with the secretory activity of signet-ring carcinoma cells is discussed.