Dendritic cells can be rapidly expanded ex vivo and safely administered in patients with metastatic breast cancer

E. Claire Dees, Karen P. McKinnon, Jennifer J. Kuhns, Kathryn A. Chwastiak, Scotty Sparks, Mary Myers, Edward J. Collins, Jeffrey A. Frelinger, Henrik Van Deventer, Frances Collichio, Lisa A. Carey, Mark E. Brecher, Mark Graham, H. Shelton Earp, Jonathan S. Serody

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

Purpose: Immunotherapy using either dendritic cells (DCs) or expanded cytotoxic T cells (CTLs) has received increased interest in the treatment of specific malignancies including metastatic breast cancer (MBC). DCs can be generated ex vivo from monocytes or CD34+ precursors. The ability to expand and safely administer CD34-derived DCs in patients with MBC that have received prior cytotoxic chemotherapy has not been evaluated. Methods: We enrolled ten patients with MBC that had received prior chemotherapy for the treatment of metastatic disease on a phase I/II trial designed to test the safety and feasibility of administering ex vivo expanded DCs from CD34 + progenitor cells. Results: Using a cocktail of multiple different cytokines, we could expand DCs 19-fold compared to the initial CD34-selected product, which allowed the administration of as many as six vaccine treatments per patient. Patients received three to six injections i.v. of DCs pulsed with either the wild type GP2 epitope from the HER-2/neu protein or an altered peptide ligand, isoleucine to leucine (I2L). Toxicity was mild, with no patients demonstrating grade III toxicity during the treatment. Two patients with subcutaneous disease had a partial response to therapy, while IFN-γ-producing CD8+ T cells could be found in two other patients during treatment. Conclusions: This approach is safe and effective in generating a significant quantity of DCs from CD34-precursors.

Original languageEnglish (US)
Pages (from-to)777-785
Number of pages9
JournalCancer Immunology, Immunotherapy
Volume53
Issue number9
DOIs
StatePublished - Sep 2004
Externally publishedYes

Keywords

  • Altered peptide ligand
  • Dendritic cell
  • HER-2/neu
  • Immunotherapy

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research

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    Dees, E. C., McKinnon, K. P., Kuhns, J. J., Chwastiak, K. A., Sparks, S., Myers, M., Collins, E. J., Frelinger, J. A., Van Deventer, H., Collichio, F., Carey, L. A., Brecher, M. E., Graham, M., Earp, H. S., & Serody, J. S. (2004). Dendritic cells can be rapidly expanded ex vivo and safely administered in patients with metastatic breast cancer. Cancer Immunology, Immunotherapy, 53(9), 777-785. https://doi.org/10.1007/s00262-004-0520-1