Allogeneic Natural Killer Cells in Patients With Advanced Metastatic Breast Cancer
We believe that administration of related allogeneic (donor) natural killer cells along with
IL-2, rather than autologous natural killer cells will provide the most effective anticancer
therapy in this setting, and wish to test this approach. To do this, we will select a
related donor who is partially HLA-matched with the study subject, to increase the
likelihood that donor natural killer cells will kill the subject's cancer cells. We will
also give chemotherapy drugs to increase the subject's tolerance for the donor natural
killer cells. We will test the use of donor natural killer (NK) cell infusions. The immune
system has a special way that it sees and identifies cancer cells or foreign agents (like
viruses). The subject's own NK cells may not attack their cancer because NK cells see the
tumor cells as "self" (a coating on the cell surface identifies a cell as "self" or
"non-self"). We have reason to believe that NK cells may not kill cancer cells because NK
cells have special receptors that "turn them off" when they encounter cancer cells (by
seeing them as "self"). We may be able to get around this problem by using donor NK cells.
Finally, subjects will receive a dose of subcutaneous IL-2 3 times a week (for 2 weeks)
which has been proven safe in our previous studies to stimulate the natural killer cells.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Number of Patients Who Had Expansion of Natural Killer Cells
Successful Natural Killer (NK) cell expansion is defined as detection of an absolute circulating donor-derived NK cell count of >100 cells/ul of whole blood 14 days after infusion with <5% donor T and B cells in mononuclear population (in metastatic breast cancer patients).
Jeffrey Miller, MD
Masonic Cancer Center, University of Minnesota
United States: Food and Drug Administration
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