CHARACTERIZATION OF MONOCLONAL-ANTIBODY PAM4 REACTIVE WITH A PANCREATIC-CANCER MUCIN

A monoclonal antibody (MAb), PAM4, having reactivity with pancreatic c arcinoma has been developed. PAM4 is an IgG(1) immunoglobulin produced by immunization of mice with mucin purified from the xenografted RIP I human pancreatic carcinoma. An immunohistochemical study of normal a dult tissues showed the PAM4 reactive epitope to be restricted to the gastrointestinal tract and absent from normal pancreas. In neoplastic tissue, PAM4 was reactive with 85% of the pancreatic carcinomas, appro ximately half of the colon cancers and none of the breast, ovarian, pr ostate, renal and liver cancers. PAM4 was, in general, non-reactive wi th pancreatitis specimens whereas CA19.9 and DUPAN2 were strongly reac tive with each one. Treatment of the mucin antigen by heating, reducti on of disulfide bonds, or protease digestion abolished immunoreactivit y with PAM4. Treatment of the mucin by neuraminidase or periodate oxid ation reduced immunoreactivity but did not completely abolish it. Our data are consistent with the proposal that the PAM4 epitope is a confo rmationally dependent peptide epitope and that certain carbohydrate st ructures are necessary in order to maintain the correct peptide confor mation. The high specificity and intense reactivity of PAM4 with pancr eatic carcinoma tissue suggests that the antibody may prove useful for in vitro diagnostic assays as well as in vivo targeting of diagnostic and therapeutic agents. (C) 1994 Wiley-Liss, Inc.