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

Journal: Cytotherapy 2006;8(3):290-8

PMID: 16793737

Full Text on Elsevier Science View on PubMed

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 autologous 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 x 10(6) DC and 15 x 10(6) 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.

Address: Division of Hematology and Department of Internal Medicine, Mayo Clinic Cancer Center, 200 First Street SW, Rochester, MN 55905, USA.

DOI: 10.1080/14653240600735743