Combination immune therapy and cytokine control therapy for cancer treatment
Compositions disclosed herein, and methods of use thereof included those for treating or preventing sepsis in a subject in need, including methods of extending of the survival of a subject suffering from sepsis, and reduction of organ dysfunction or failure due to sepsis. Methods of treating or preventing sepsis in a subject in need includes administering compositions comprising early apoptotic cells or early apoptotic cell supernatants. Compositions and methods of use thereof may reduce the negative proinflammatory effect accompanying sepsis. Further, anti-inflammatory cytokine release may be reduced. In certain instances, compositions may include additional agents.
1. A method of treating, preventing, inhibiting, reducing the incidence of, ameliorating, or alleviating sepsis, or any combination thereof, in a human subject in need, comprising the step of administering a composition comprising an early apoptotic cell population to said subject, said early apoptotic cell population comprising a mononuclear enriched cell population comprising ≥40% AnnexinV+ and ≤15% propidium iodide+ cells, wherein the source of sepsis is selected from pneumonia, endovascular, methicillin-resistant Staphylococcus aureus (MRSA) infection, a urinary tract infection (UTI), or a biliary tract infection, and wherein said administering treats, prevents, inhibits, reduces the incidence of, ameliorates, or alleviates sepsis in said subject.
2. The method of claim 1 , wherein sepsis comprises mild, severe, acute, or highly aggressive sepsis.
3. The method of claim 1 , wherein the survival of said subject is increased.
4. The method of claim 1 , wherein said method reduces the incidence of organ failure or organ dysfunction, or organ damage, or a combination thereof.
5. The method of claim 4 , wherein organ failure comprises acute multiple organ failure.
6. The method of claim 1 , wherein said mononuclear early apoptotic cell population comprises
decreased non-quiescent non-apoptotic cells, a suppressed cellular activation of any living non-apoptotic cells, or a reduced proliferation of any living non-apoptotic cells, or any combination thereof.
7. The method of claim 1 , wherein said early apoptotic cell population comprises a pooled population of early apoptotic cells.
8. The method of claim 1 , wherein said administering comprises a single infusion of said early apoptotic cell population.
9. The method of claim 1 , wherein said administering comprises at least two infusions of said apoptotic cell population, wherein the second infusion is administered 48 hours±6 hours after the first infusion.
10. The method of claim 1 , wherein said administering comprises intra venal administration.
11. The method of claim 1 , further comprising administering an additional therapy.
12. The method of claim 11 , wherein said additional therapy is administered prior to, concurrent with, or following administration of said early apoptotic cells.
13. The method of claim 1 , wherein said method comprises a first-line therapy.
14. The method of claim 1 , wherein said method comprises an adjuvant therapy.
15. The method of claim 1 , wherein said method comprises rebalancing the immune response of said subject.
16. The method of claim 15 , wherein said rebalancing comprises reducing the secretion of one or more proinflammatory cytokine/chemokine.
17. The method of claim 15 , wherein said rebalancing comprises reducing the secretion of one or more anti-inflammatory cytokine/chemokine.
18. The method of claim 15 , wherein said rebalancing comprises reducing secretion of one or more pro-inflammatory cytokines/chemokines and one or more anti-inflammatory cytokines/chemokines.
19. The method of claim 1 , wherein said method prevents, inhibits, reduces the incidence of, or reduces the severity of a cytokine and chemokine storm in said subject.
20. The method of claim 1 , wherein said administration comprises two infusions of said composition of early apoptotic cells, and wherein each infusion comprises about 140×10 6 cells/Kg±20%.