TUMOR-ASSOCIATED ANTIGENS RECOGNIZED BY HUMAN MONOCLONAL-ANTIBODIES

Background: Nonhuman monoclonal antibodies (MoAbs) of desired specific ities have been studied in cancer treatment and tumor targeting with m inimal success. Attempts of using humanized chimeric antibodies have n ot improved significantly their clinical applications. We have engaged in the development of human MoAbs by incorporating the in vitro immun ization protocols to the nodal lymphocytes of cancer patients. Three h uman MoAbs thus generated were found to be strongly reactive with vari ous human malignancies. The antigens recognized by the three antibodie s were selected for immunochemical and biochemical characterizations. Methods: The antigens investigated were AgSK1, PA 1-2 and PA 3-1. The patterns of each antigen expression in various human cancer celt lines were studied by the immunocytochemical staining technique. The expres sion of AgSK1 in association with cellular proliferation was examined by the flow cytometry analysis. In studying the biochemical natures of these antigens, their sensitivies toward various chemical and physica l treatments were determined. The antigens that were shown to be prote ins were subjected to SDS-PAGE and Western blot for estimations of mol ecular weights. Results: The AgSK1 was detected in 10 human carcinoma cell lines but in none of the melanoma cell lines. This suggests that SK1 may be an epithelial or carcinoma marker. The phenotypic expressio ns of AgSK1 were shown to be associated with proliferation of carcinom a cells. Biochemically AgSK1 was a sialophycoprotein with an estimated molecular weight of 42-44 kilodaltons (kDa). HuMAb PA1-2 demonstrated a unique staining pattern at both the cytoplasmic and intercellular i nterface. The stained filamentlike structures extending from cell to c ell indicated that Ag PA1-2 might play a role in cellular interactions . Biochemically, Ag PA1-2 appeared to be an asialocarbohydrate. The Ag PA3-1 was a cytoplasmic glycoprotein expressed by all 13 cell lines. The estimated molecular weights of PA3-1 were 164, 104, and 40 kDa. Co nclusions: Tumor-associated antigens recognized by the human MoAbs may be more relevant clinically than those recognized by the mouse immune system. Carcinoma-specific human MoAbs are desirable for cancer treat ment and tumor localization.