Induction of cytotoxic T-lymphocyte responses in vivo after vaccinations with peptide-pulsed dendritic cells

Vaccination of patients with cancer using dendritic cells (DCs) was shown t o be effective for B-cell lymphoma and malignant melanoma, Here we provide evidence that patients with advanced breast and ovarian cancer can be effic iently vaccinated with autologous DCs pulsed with HER-2/neu- or MUC1-derive d peptides. Ten patients were included in this pilot study. The DC vaccinat ions were well tolerated with no side effects. In 5 of 10 patients, peptide -specific cytotoxic T lymphocytes (CTLs) could be detected in the periphera l blood using both intracellular IFN-gamma staining and Cr-51-release assay s. The major CTL response in vivo was induced with the HER-2/neu-derived E7 5 and the MUC1-derived M1.2 peptide, which lasted for more than 6 months, s uggesting that these peptides might be immunodominant. In addition, in one patient vaccinated with the MUC1-derived peptides, CEA- and MAGE-3 peptide- specific T-cell responses were detected after several vaccinations. In a se cond patient immunized with the HER-2/neu peptides, MUC1-specific T lymphoc ytes were induced after 7 immunizations, suggesting that antigen spreading in vivo might occur after successful immunization with a single tumor antig en. Our results show that vaccination of DCs pulsed with a single tumor ant igen may induce immunologic responses in patients with breast and ovarian c ancer. This study may be relevant to the design of future clinical trials o f other peptide-based vaccines. (C) 2000 by The American Society of Hematol ogy.