Testing the safety of clinical-grade mature autologous myeloid DC in a phase I clinical immunotherapy trial of CML

M. R. Litzow, A. B. Dietz, P. A. Bulur, G. W. Butler, D. A. Gastineau, A. Hoering, S. R. Fink, L. Letendre, D. J. Padley, S. F. Paternoster, A. Tefferi, S. Vuk-Pavlović

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Background: We conducted a phase I clinical immunotherapy trial of CML to evaluate the safety of a clinical-grade leukemic DC product standardized for purity and mature phenotype. Methods: We injected auto logous DC into patients in late chronic or accelerated phases of CML. The patients received mature CD83+ and bcr-abl+ DC prepared from CD14+ cells. Two cohorts of three patients received four injections each of 3 × 106 DC and 15 × 106 DC/injection, respectively. The first patient was studied before imatinib mesylate (IM) was available, four patients were treated concurrently with IM therapy and one did not tolerate the IM and was off the drug at the time of DC therapy. IM effects on WBC counts precluded DC preparation in numbers sufficient for further dose escalation. The first patient received DC s.c. and all subsequent patients received DC into a cervical lymph node under ultrasound guidance. Results: DC injections were well tolerated. We observed no clinical responses. T cells drawn later in the course of therapy were more sensitive to stimulation by CML DC in vitro. Discussion: The increase in T-cell sensitivity to CML-specific stimulation that accompanied active immunization by CML DC justifies further clinical studies, possibly with modifications such as an increased frequency and number of DC injections.

Original languageEnglish (US)
Pages (from-to)290-298
Number of pages9
JournalCytotherapy
Volume8
Issue number3
DOIs
StatePublished - May 1 2006

Keywords

  • CML
  • DC
  • Immunotherapy
  • T cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Genetics(clinical)
  • Cell Biology
  • Cancer Research
  • Transplantation

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    Litzow, M. R., Dietz, A. B., Bulur, P. A., Butler, G. W., Gastineau, D. A., Hoering, A., Fink, S. R., Letendre, L., Padley, D. J., Paternoster, S. F., Tefferi, A., & Vuk-Pavlović, S. (2006). Testing the safety of clinical-grade mature autologous myeloid DC in a phase I clinical immunotherapy trial of CML. Cytotherapy, 8(3), 290-298. https://doi.org/10.1080/14653240600735743