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.
Original language | English |
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Journal | Cancer immunology, immunotherapy |
Volume | 56 |
Issue number | 9 |
Pages (from-to) | 1485-99 |
Number of pages | 15 |
ISSN | 0340-7004 |
DOIs | |
Publication status | Published - Sept 2007 |
Keywords
- Adipokines
- Adult
- Aged
- Biomarkers, Tumor/blood
- Breast Neoplasms/immunology
- Cancer Vaccines/therapeutic use
- Chitinase-3-Like Protein 1
- Dendritic Cells/immunology
- Female
- Glycoproteins/blood
- Humans
- Interleukin-6/blood
- Lectins
- Middle Aged
- Peptide Fragments/immunology
- Tumor Suppressor Protein p53/immunology
- Vaccination