ANTI-MUC1 CLASS-I RESTRICTED CTLS IN METASTATIC BREAST-CANCER PATIENTS IMMUNIZED WITH A SYNTHETIC MUC1 PEPTIDE

Sixteen metastatic breast cancer patients were immunized with a low do se (5 mu g) of a 16 amino acid MUC1 peptide (GVTSAPDTRPAPGSTA) conjuga ted to KLH (BP16-KLH) plus DETOX adjuvant and evaluated for antibody t iters against MUC1 peptide and KLH and for cytotoxic lymphocyte (CTL) activity using class I HLA-matched MUC1-positive tumor targets. All pa tients generated strong anti-KLH IgG responses. Only 3 patients develo ped an anti-MUC1 IgG response, which was weak in magnitude. As it is c ontroversial whether human cancer patients generate class-I-restricted CTL against MUC1 we examined anti-MUC1 CTL activity of PBLs following 4 immunizations with BP 16-KLH. The generation of MUC1-specific CTLs required only a 6-day in vitro stimulation of patients' T-cells with s ynthetic MUC1-peptide-pulsed autologous APCs, The assay for CTL activi ty was a 4 hr Cr-51 release from labeled adenocarcinoma target cells. Eleven of the 16 immunized patients were tested for CTL activity using class-I-matched adenocarcinoma target cell lines. Evidence for class- I-restricted killing of MUC1-expressing tumor cell lines was obtained in 7 of these 11 patients. (C) 1998 Wiley-Liss, Inc.