TAG-72-REACTIVE ANTIBODY CC49 RECOGNIZES MOLECULES EXPRESSED BY HEMATOPOIETIC-CELL LINES

Aberrant glycosylation of mucins on the surface of adenocarcinomas lea ds to exposure of novel tumor-associated epitopes potentially recogniz able by the immune system. Monoclonal antibodies (mAbs) have been deve loped against some of these epitopes, One such mAb, denoted CC49, reco gnizes the tumor-associated glycoprotein TAG-72, Most adenocarcinomas, including breast, colon, ovarian, prostate, and gastric, express some form of this molecule, recognizable by the CC49 antibody. The widespr ead distribution of the antigen on transformed cells makes the CC49 mA b a potentially powerful tool in numerous immunotherapy contexts, In t he course of our studies with CC49 and certain of its molecularly engi neered derivatives, we screened a number of human hematopoietic cell l ines for TAG-72 expression by flow cytometry using CC49, We found that the T-cell line, Jurkat, had a higher level of CC49 mAb binding than any of the carcinoma cell lines previously evaluated in our laboratory . In addition, the myelomonocytic cell line Tf-1 and the erythroleukem ia cell line K562 were also positive for CC49 mAb binding by flowcytom etric analysis, However; peripheral blood lymphocytes and certain othe r hematopoietic cell lines were not able to bind the CC49 mAb, Immunob lot analyses of cell extracts from the CC49 reactive lines indicated d istinct protein species reactive with the CC49 antibody. In some insta nces, cells expressing these reactive proteins were susceptible to ant ibody-dependent cellular cytotoxicity using a chimeric derivative of t he CC49 antibody. These results indicate that the cell membrane expres sion of molecules recognized by CC49 extends beyond adenocarcinomas to certain cell lines of hematopoietic origin.