CYTOTOXIC T-CELLS FROM OVARIAN MALIGNANT-TUMORS CAN RECOGNIZE POLYMORPHIC EPITHELIAL MUCIN CORE PEPTIDES

CTL isolated from tumor infiltrating lymphocytes/tumor associated lymp hocytes (TAL) infiltrating ovarian tumors have been demonstrated to me diate lysis of tumor targets after in vitro culture. These effector ce lls are of particular interest as cellular probes to detect and define human tumor Ag and epitopes that stimulate cellular immunity to human tumors. Polymorphic epithelial mucin (PEM) core peptides are potentia l candidates as tumor specific Ag because of their preferential expres sion on epithelial tumors. We report here that ovarian CTL-TAL can rec ognize mucin (Muc-1) core peptide of PEM. Several ovarian CTL-TAL line s were developed that recognized in a non-MHC restricted fashion an Mu c-1+ ovarian tumor, but not an Muc-1- tumor. To define the specificity of these CTL-TAL and exclude cross-reactivity with other potential Ag , cytotoxicity experiments were performed using as targets EBV-transfo rmed cell lines with an expression construct containing the Muc.1 cDNA . These ovarian CTL-TAL lysed mucin core-peptide transfected cells but not targets transfected with an expression construct containing a muc in frame-shift mutant cDNA as control. In addition, targets pulsed wit h short synthetic peptides composed of amino acids 1-1 4 of the Muc 1 core peptide repeat were also lysed by the same CTL-TAL. This lysis wa s inhibited by the mAb SM3 that recognize an epitope on the mucin core peptide. These results, which are a demonstration of a specific Ag re cognized by ovarian CTL-TAL, may be of interest for specific immunothe rapy of ovarian cancer.