Allogeneic Natural Killer (NK) 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.

Inclusion criteria:

- Diagnosis of metastatic breast cancer that has progressed on or failed at least one
salvage chemotherapy regimen for metastatic disease and that meets the following
disease specific related criteria:

- Measureable metastatic disease per Response Evaluation Criteria In Solid Tumor
(RECIST) - bone only not eligible.

- Disease progression while receiving prior therapy with a hormonal agent (if
estrogen/progesterone receptor-positive) and/or trastuzumab (Herceptin®) (if
HER2-neu positive)

- Brain metastases allowed provided they are stable for ≥ 3 months after prior
treatment

- Related HLA-haploidentical natural killer cell donor available (by ≥ class I serologic
typing)

- Male or female

- Performance status 50-100%

- Platelet count ≥ 80,000/mm³ (unsupported by transfusions)

- Hemoglobin ≥ 9 g/dL (unsupported by transfusions)

- Absolute neutrophil count ≥ 1,000/mm³ (unsupported by sargramostim [GM-CSF] or
filgrastim [G-CSF])

- Creatinine ≤ 2.0 mg/dL

- Liver function tests < 5 times normal

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- LVEF > 40%*

- Pulmonary function > 50%* (DLCO corrected AND FEV_1)

- No active infection (i.e., afebrile, off antibiotics, and no uninvestigated radiologic
lesions)

Exclusion Criteria:

- At least 3 days since prior prednisone or other immunosuppressive medications

- No other concurrent therapy for cancer