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.
Pathology Institute, University of Wurzburg, Federal Republic of Germany.
M
M
Pfaff
R
R
O'Connor
H P
HP
Vollmers
H K
HK
Müller-Hermelink
D002288:Adenocarcinoma, Mucinous / Q000276:immunology / Q000473:pathology*; D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm / Q000032:analysis* / Q000276:immunology; D015153:Blotting, Western; D002460:Cell Line; D015180:Electrophoresis, Gel, Two-Dimensional; D005455:Fluorescent Antibody Technique; D006801:Humans; D007118:Immunoassay; D007124:Immunoenzyme Techniques; D007633:Keratins / Q000032:analysis / Q000276:immunology; D008970:Molecular Weight; D009363:Neoplasm Proteins / Q000032:analysis* / Q000276:immunology; D012016:Reference Values; D013274:Stomach Neoplasms / Q000276:immunology / Q000473:pathology*
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D009363:Neoplasm Proteins; D007633:Keratins