Enhancement of the anti-tumor activity of a peripheral blood progenitor cell graft by mobilization with interleukin 2 plus granulocyte colony- stimulating factor in patients with advanced breast cancer

Linda J. Burns, Daniel J. Weisdorf, Todd E. Defor, Tanya L. Repka, Kathleen M. Ogle, Cara Hummer, Jeffrey S. Miller

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Objective. Autologous interleukin 2 (IL-2)-activated natural killer (NK) cells kill a broad spectrum of tumor targets, including breast cancer. We hypothesized that mobilization with IL-2 and granulocyte colony-stimulating factor (G-CSF) for collection of peripheral blood progenitor cells (PBPC) may enhance the anti-tumor activity of the graft in autograft recipients. We determined the dose-limiting toxicity and maximum tolerated dose of subcutaneous IL-2 given with G-CSF for PBPC mobilization, the ability of IL-2 + G-CSF mobilized stem cells to reconstitute hematopoiesis, and the in vitro immunologic function of the graft in patients with advanced breast cancer. Materials and Methods. Forty-three women with stage IIIA/B or metastatic breast cancer underwent mobilization of PBPC with IL-2 administered subcutaneously for 14 days along with G-CSF for the latter 7 days. IL-2 was given in a dose-escalated manner, with the maximum tolerated dose determined to be 1.75 x 106 IU/m2/day. Fifteen women with stage IIIA/B or metastatic breast cancer underwent G-CSF mobilization alone and served as a control group. Fifty-two percent of the patients mobilized with IL-2 at the maximum tolerated dose reached the target number of CD34+ cells for transplantation with three aphereses compared to 93% of control patients who were mobilized with G-CSF alone. Results. There was no significant impact on time to engraftment of neutrophils or platelets using either mobilization regimen. The addition of subcutaneous IL-2 to mobilization increased the cytotoxicity of IL-2-activated mononuclear cells from the PBPC product against the breast cancer cell target, MCF-7, and increased the percentage of NK cells and activated T cells in the PBPC product. The enhanced NK cell number was sustained in the early posttransplant period. IL-2 + G-CSF mobilization is safe, may lead to a more immunologically functional graft without impairing hematologic recovery, and thus merits further exploration to evaluate the clinical anti-tumor efficacy of these immunocompetent grafts. Conclusions. Limitations of this combined approach to stem cell mobilization include a decrease in the number of CD34+ cells mobilized with the combined cytokines and the short duration of the increased number of anti-tumor effector cells after transplant.

Original languageEnglish (US)
Pages (from-to)96-103
Number of pages8
JournalExperimental Hematology
Volume28
Issue number1
DOIs
StatePublished - Jan 2000

Bibliographical note

Funding Information:
We thank Juliette Gay, R.N., for providing assistance in patient care, and Roby Nicklow, R.N., and Eva Gallagher, R.N., for data management. L.J.B. is the recipient of a Department of Defense Career Development Award and a grant from the Minnesota Medical Foundation. We also acknowledge the support of the Bone Marrow Transplant Research Fund of the University of Minnesota and the Masonic Order of the Eastern Star.

Keywords

  • Breast cancer
  • Granulocyte colony-stimulating factor
  • Interleukin 2
  • Mobilization
  • Peripheral blood progenitor cells

Fingerprint

Dive into the research topics of 'Enhancement of the anti-tumor activity of a peripheral blood progenitor cell graft by mobilization with interleukin 2 plus granulocyte colony- stimulating factor in patients with advanced breast cancer'. Together they form a unique fingerprint.

Cite this