Linked Life Data

17285289

Source:http://linkedlifedata.com/resource/pubmed/id/17285289

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pubmed-article:17285289pubmed:abstractTextp53 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.lld:pubmed
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pubmed-article:17285289pubmed:dateRevised2011-11-17lld:pubmed
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pubmed-article:17285289pubmed:articleTitleVaccination 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.lld:pubmed
pubmed-article:17285289pubmed:affiliationDepartment of Oncology, Copenhagen University Hospital, Herlev, Denmark. inge.m.svane@dadlnet.dklld:pubmed
pubmed-article:17285289pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:17285289pubmed:publicationTypeResearch Support, Non-U.S. Gov'tlld:pubmed
pubmed-article:17285289pubmed:publicationTypeClinical Trial, Phase IIlld:pubmed
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