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 endogenous effector cells at the site; and
administering a composition of activated NK cells at a dose effective to deplete the cancer stem cell, wherein the activated NK cells are enriched from peripheral blood and activated by culture in the presence of IL-2, anti-CD16 antibodies, sonicated probiotic bacteria, and osteoclasts.
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 2 , wherein the cancer stem cells are adenocarcinoma stem cells.
5. The method of claim 1 , wherein endogenous 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 endogenous 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 injected at the site of the tumor.
10. The method of claim 1 , further comprising administering to the individual a chemotherapeutic agent that depletes differentiated cancer cells.
11. The method of claim 10 , wherein the chemotherapeutic agent is 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 , wherein the NK cells are cultured with sonicated probiotic bacteria at a cell:cell ratio of from 10:1 to 1:10.
14. The method of claim 1 , wherein the sonicated probiotic bacteria comprise Streptococcus thermophilus, Bifidobacterium longum , and Bifidobacterium breve.
15. The method of claim 1 , wherein the sonicated probiotic bacteria comprise Streptococcus thermophilus, Bifidobacterium longum, Bifidobacterium breve, Bifidobacterium infantis, Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus casei , and Lactobacillus bulgaricus.
16. A method for depleting cancer stem cells at a tumor site in an individual, the method comprising:
depleting endogenous effector cells at the site; and
administering a composition of activated NK cells at a dose effective to deplete the cancer stem cell, wherein the NK cells are the NK cells are enriched from peripheral blood and activated by culture in the presence of IL-2, anti-CD16 antibodies, sonicated probiotic bacteria, and osteoclasts; and
further sequentially administering to said individual NK cells treated with IL-2 and/or IL-12, or IFN-α, in the presence of anti-CD16 antibody to induce split anergy, in a dose effective to support differentiation of cancer stem cells.