High dose chemotherapy and autologous stem cell transplantation (BMT) is widely used in the treatment of advanced breast cancer. However, the procedure is followed by a high relapse rate, and its overall efficacy and place in the treatment of breast cancer of varying stages is still evolving. We have developed approaches for induction of a graft versus tumor (GVT) effect following autologous BMT. Our preclinical studies have shown that incubation of peripheral stem cells (PBSC) with Interleukin-2 (IL-2) in vitro leads to the generation of killer cells within the PBSC population. BMT with these activated cells (APC) followed by IL-2 therapy induces a GVT effect in animal models, which appears to correlate with certain immunological changes. We have already initiated a phase I clinical protocol based upon these results in patients with stage Il, III, and IV breast cancer. Interestingly, these patients have circulating cells capable of lysing tumor and also have evidence on biopsy of autologous graft versus host disease (GVH) even in visceral organs. We have also found that IL-2 activated primed peripheral blood stem cells will engraft within 10-12 days. Thus, we have been able to translate our initial preclinical and animal model results into the clinic. This proposal aims to investigate the efficacy of this approach in a randomized trial of high dose chemotherapy plus """"""""activated"""""""" PBSC and the optimum IL-2 regimen versus high dose chemotherapy plus standard PBSC in which the primary comparison is disease-free survival time and the incidence of GVH will be evaluated. We will also evaluate the mechanisms and interrelationships between GVH and GVT with respect to cell phenotype, T-cell receptors and cytokines induced, similar to our studies in the animal model.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center (P50)
Project #
3P50CA058185-07
Application #
6269566
Study Section
Project Start
1998-09-01
Project End
1999-08-31
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
7
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Georgetown University
Department
Type
DUNS #
049515844
City
Washington
State
DC
Country
United States
Zip Code
20057
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