Resistance to multiple chemotherapeutic agents is a common clinical problem in the treatment of cancer. This resistance may occur before primary therapy or be acquired during treatment. We have generated a monoclonal antibody (MAb) (JSB-I), specific for a conserved epitope on the plasma membrane 170- to 180-kDa glycoprotein, the expression of which is strongly correlated with the degree of multi-drug resistance (MDR). JSB-I strongly binds to both Chinese-hamster-derived MDR cell lines and human MDR cell lines, including cell lines derived from lung and ovary. A drug-sensitive revertant line, and the corresponding drug-sensitive parent lines, showed only weak reactivity or none at all. JSB-I reacts strongly to air-dried or acetone-fixed cells and therefore has potential value for diagnostic detection of MDR cells in human tumor samples.

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Using viable cells of a human squamous-cell carcinoma (SCC) cell line as immunogen, we generated 2 monoclonal antibodies, MAbs K984 and K928, to SCC surface antigens. Immunoperoxidase staining of frozen sections of normal epidermis revealed that MAb K984 reacts with the poorly differentiated basal cells, while MAb K928 is reactive with the more highly differentiated suprabasal cells. A similar complementary reaction pattern of these antibodies was demonstrated in the majority of well-differentiated human tumors and some moderately differentiated SCCs. In contrast, simultaneous reactivity of MAb K984 and K928 was found for the majority of cells within other well- and moderately differentiated SCCs, as well as all poorly differentiated SCCs. Further biochemical characterization indicated that the antigen recognized by MAb K984 is similar to the one recognized by MAb SF-25. MAb K928 recognizes a 50- to 55-kDa molecule under non-reducing conditions. Antibodies with similar features to MAb K928 have not been described previously. The antigens recognized by MAbs K984 and K928 can be regarded as novel markers associated with cellular maturation in squamous epithelia. The antigen detected by MAb K984 is probably associated with the proliferating fraction in SCCs.

During our efforts to develop monoclonal antibodies (MAbs) to tumor associated surface antigens of squamous cell carcinomas of the head and neck, monoclonal antibody K 931 was produced. The high affinity antibody (Ka 5.0 x 10(10) M-1) showed reactivity with 58 out of 62 squamous cell carcinomas of the head and neck. In contrast normal squamous epithelium as found in epidermis, oral cavity, epiglottis, pharynx, larynx and esophagus did not express the antigen. All other tested epithelial (simple and transitional) tissues did express the antigen, but non-epithelial tissues were negative. Further characterization revealed that the antigen represents the 17-1A antigen. A not earlier reported, enhanced expression of the 17-1A antigen was observed among some primary and all metastatic SCC.