Depletion of cancer stem cells
Compositions and methods are provided for killing of cancer stem cells, and for the transplantation of pluripotent stem cells and differentiated cells derived therefrom.
1 . A method for depleting cancer stem cells at a tumor site in an individual, the method comprising:
depleting effector cells at the site; and
administering a composition of activated NK cells at a dose effective to deplete the cancer stem cells.
2 . The method of claim 1 , wherein the cancer stem cells are carcinoma stem cells.
3 . The method of claim 2 , wherein the carcinoma is a squamous cell carcinoma.
4 . The method of claim 3 , wherein said cancer stem cells are identified by expression of one or both of CD44 and CD133.
5 . The method of claim 1 , wherein effector cells are depleted by a dose of radiation sufficient to substantially eliminate monocytes in the tumor microenvironment.
6 . The method of claim 1 , wherein effector cells are depleted by a dose of chemotherapy sufficient to substantially eliminate monocytes in the tumor microenvironment.
7 . The method of claim 1 , wherein the NK cells are autologous.
8 . The method of claim 1 , wherein the NK cells are allogeneic.
9 . The method of claim 1 , wherein the NK cells are enriched from a peripheral blood sample and activated by culture in the presence of IL-2, optionally with additional IL12 or interferon alpha.
10 . The method of claim 1 , wherein the NK cells are injected at the site of the tumor.
11 . The method of claim 1 , further comprising administering to the individual an effective dose of a taxane and N-acetylcysteine.
12 . The method of claim 11 , wherein the taxane is paclitaxel.
13 . The method of claim 1 , further comprising administering to the individual a chemotherapeutic agent that depletes differentiated cancer cells.
14 . A method for depleting cancer stem cells at a tumor site in an individual, the method comprising:
administering a combination of an effective dose of a taxane and N-acetylcysteine.
15 . The method of claim 14 , wherein the taxane is paclitaxel.
16 . The method of claim 14 , wherein the cancer stem cells are carcinoma stem cells.
17 . The method of claim 16 , wherein the carcinoma is a squamous cell carcinoma.
18 . A method for establishing tolerance to a stem cell graft, the method comprising administering an anti-CD16 antibody to tolerize NK cells to support differentiation of stem cells.
19 . The method of claim 16 , wherein NK cells are treated with IL-2 and/or IL-12, or IFN-α in the presence of anti-CD16 antibody to induce split anergy.
20 . A method of claim 18 for establishing tolerance to a stem cell graft, the method comprising introducing stem cells mixed with monocytes for engraftment.