Establishment of an anti-A human monoclonal antibody from a blood group A lung cancer patient: evidence for the occurrence of autoimmune response to difucosylated type-2 chain A

Abstract

A human monoclonal antibody, NCC-HAL-27, has been established by a combination of transformation by Epstein-Barr virus (EBV) and a newly devised "micro cell fusion" technique. Lymphocytes used were derived from a blood group A lung cancer patient. Cancer cells, as well as normal epithelial cells of lung, stomach and colon (including autologous tissue) from blood group A individuals, fixed in formalin, were immunohistochemically stained by the antibody. A higher concentration (greater than 140 mg/ml) of the antibody agglutinated only type-A (not B or 0) erythrocytes. The structural specificity of NCC-HAL-27 was determined by particle-concentrated fluorescence immunoassay and thin-layer chromatography immunostaining using purified, well-defined glycolipids. The antibody was found to be directed against type-2 chain A and difucosylated type-2 chain A antigens with no cross-reactivity with known A-like antigens, such as Tn and Forssman antigen, generally expressed irrespective of ABO status. Interestingly, however, the antibody detected the expression of incompatible A antigen in colon cancers of B and 0 individuals with high incidence (30%-40%). The finding that a monoclonal antibody generated from a blood group A cancer-bearing host is directed against autologous A antigen is novel because the ABO blood group antigens are the major alloantigens in man, with strictly controlled immunotolerance. The induction of anti-A in this patient could, therefore, be directly associated with the lung cancer.