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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

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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 × 106 p53-peptide loaded DC with 1–2 weeks interval. Concomitantly, 6 MIU/m2 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.

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Acknowledgment

This work was supported by grants from Dansk Kræftforsknings Fond, The Danish Cancer Society, Direktør Leo Nielsen og Hustru Karen Margrethe Nielsens Legat for Lægevidenskabelig Grundforskning, Michaelsen Fonden, and Aase og Ejnar Danielsens Fond.

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Authors and Affiliations

  1. Department of Oncology, Copenhagen University Hospital, Herlev, Denmark

    Inge Marie Svane, Dorte Nielsen & Claus Kamby

  2. Center for Cancer Immune Therapy, Department of Hematology, Copenhagen University Hospital, Herlev, Denmark

    Inge Marie Svane, Hans E. Johnsen, Eva Gaarsdal & Kirsten Nikolajsen

  3. Department of Rheumatology, Copenhagen University Hospital, Herlev, Denmark

    Julia S. Johansen

  4. Department of Pathology, Copenhagen University Hospital, Herlev, Denmark

    Eva Balslev

  5. Department of Medical Anatomy, The Panum Institute, University of Copenhagen, Copenhagen, Denmark

    Anders E. Pedersen & Mogens H. Claesson

  6. Department of Oncology, Roskilde Hospital, Roskilde, Denmark

    Svend Ottesen

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  1. Inge Marie Svane
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  2. Anders E. Pedersen
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Correspondence to Inge Marie Svane.

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Svane, I.M., Pedersen, A.E., Johansen, J.S. et al. 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. Cancer Immunol Immunother 56, 1485–1499 (2007). https://doi.org/10.1007/s00262-007-0293-4

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