Methods of conditioning patients for T cell therapy
The invention provides methods of increasing the efficacy of a T cell therapy in a patient in need thereof. The invention includes a method of conditioning a patient prior to a T cell therapy, wherein the conditioning involves administering a combination of cyclophosphamide and fludarabine.
1. A method of treating a patient having a tumor comprising administering to the patient, at day zero, a therapeutically effective amount of chimeric antigen receptor (CAR) T cells from about 1×10 6 to about 5×10 6 engineered CAR T cells/kg, wherein the tumor has been exposed to a single dose of cyclophosphamide from about 900 mg/m 2 to about 1000 mg/m 2 and one or more doses of fludarabine of about 25 mg/m 2 /day, about 30 mg/m 2 /day, about 35 mg/m 2 /day, about 40 mg/m 2 /day, about 45 mg/m 2 /day, or about 50 mg/m 2 /day and wherein the patient has been determined to exhibit a higher serum level of IL-15 and MCP-1 on day zero, prior to CAR T cell administration, than at baseline, which is prior to tumor exposure to cyclophosphamide and fludarabine.
2. The method of claim 1 , wherein the therapeutically effective amount of CAR T cells is about 1×10 6 or about 2×10 6 cells/kg.
3. The method of claim 1 , wherein the tumor is a leukemia or a lymphoma.
4. The method of claim 1 , wherein the dose of fludarabine is 25 mg/m 2 /day.
5. The method of claim 1 , wherein the patient has acute lymphoblastic leukemia (ALL).
6. The method of claim 1 , wherein the administration of cyclophosphamide and/or fludarabine begins at least about five days prior to administration of the CAR T cells (day 0).
7. The method of claim 1 , wherein the CAR T cells express a chimeric antigen receptor that comprises an scFv antibody, wherein the scFv antibody is capable of binding a tumor antigen.
8. The method of claim 7 , wherein the tumor antigen is CD19.
9. The method of claim 1 , wherein the dose of fludarabine is administered daily for three days.
10. The method of claim 1 , wherein the dose of cyclophosphamide and one of the doses of fludarabine are administered on the same day.
11. The method of claim 1 , wherein the dose of cyclophosphamide is administered at least about one day before the dose of fludarabine.
12. The method of claim 1 , wherein the dose of fludarabine is administered at least about one day before the dose of cyclophosphamide.
13. The method of claim 1 , wherein the therapeutically effective amount of CAR T cells is about 2×10 6 engineered CAR T cells/kg.
14. The method of claim 1 , wherein the dose of cyclophosphamide is about 900 mg/m 2 .
15. The method of claim 14 , wherein one of the doses of fludarabine is about 25 mg/m 2 /day or about 30 mg/m 2 /day.