@article{b5fdf5c0ac0011ddb5e9000ea68e967b,
title = "Vaccination with p53 peptide-pulsed dendritic cells is associated with disease stabilization in patients with p53 expressing advanced breast cancer; monitoring of serum YKL-40 and IL-6 as response biomarkers.",
abstract = "p53 Mutations are found in up to 30% of breast cancers and peptides derived from over-expressed p53 protein are presented by class I HLA molecules and may act as tumor-associated epitopes in cancer vaccines. A dendritic cell (DC) based p53 targeting vaccine was analyzed in HLA-A2+ patients with progressive advanced breast cancer. DCs were loaded with 3 wild-type and 3 P2 anchor modified HLA-A2 binding p53 peptides. Patients received up to 10 sc vaccinations with 5 x 10(6) p53-peptide loaded DC with 1-2 weeks interval. Concomitantly, 6 MIU/m(2) interleukine-2 was administered sc. Results from a phase II trial including 26 patients with verified progressive breast cancer are presented. Seven patients discontinued treatment after only 2-3 vaccination weeks due to rapid disease progression or death. Nineteen patients were available for first evaluation after 6 vaccinations; 8/19 evaluable patients attained stable disease (SD) or minor regression while 11/19 patients had progressive disease (PD), indicating an effect of p53-specific immune therapy. This was supported by: (1) a positive correlation between p53 expression of tumor and observed SD, (2) therapy induced p53 specific T cells in 4/7 patients with SD but only in 2/9 patients with PD, and (3) significant response associated changes in serum YKL-40 and IL-6 levels identifying these biomarkers as possible candidates for monitoring of response in connection with DC based cancer immunotherapy. In conclusion, a significant fraction of breast cancer patients obtained SD during p53-targeting DC therapy. Data encourage initiation of a randomized trial in p53 positive patients evaluating the impact on progression free survival.",
author = "Svane, {Inge Marie} and Pedersen, {Anders E} and Johansen, {Julia S} and Johnsen, {Hans E} and Dorte Nielsen and Claus Kamby and Svend Ottesen and Eva Balslev and Eva Gaarsdal and Kirsten Nikolajsen and Claesson, {Mogens H}",
note = "Keywords: Adult; Aged; Breast Neoplasms; Cancer Vaccines; Dendritic Cells; Female; Glycoproteins; Humans; Interleukin-6; Middle Aged; Peptide Fragments; Tumor Markers, Biological; Tumor Suppressor Protein p53; Vaccination",
year = "2007",
doi = "10.1007/s00262-007-0293-4",
language = "English",
volume = "56",
pages = "1485--99",
journal = "Cancer Immunology, Immunotherapy",
issn = "0340-7004",
publisher = "Springer",
number = "9",
}
