Methods of conditioning patients for t cell therapy
AssigneesKite Pharma, Inc., The United States of America, as represented by the Secretary, Department of Health and Human Services
InventorsAdrian BOT, Jeffrey WIEZOREK, William GO, Rajul JAIN, James N. KOCHENDERFER, Steven A. ROSENBERG
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Abstract
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.
Claims113
A method of conditioning a patient in need of a T cell therapy comprising administering to the patient a dose of cyclophosphamide between 200 mg/m2/day and 2000 mg/m2/day and a dose of fludarabine between 20 mg/m2/day and 900 mg/m2/day.
A method of reducing endogenous lymphocytes in a patient in need of a T cell therapy comprising administering to the patient a dose of cyclophosphamide between 200 mg/m2/day and 2000 mg/m2/day and a dose of fludarabine between 20 mg/m2/day and 900 mg/m2/day.
A method of increasing a serum level of a homeostatic cytokine in a patient in need of a T cell therapy comprising administering to the patient a dose of cyclophosphamide between 200 mg/m2/day and 2000 mg/m2/day and a dose of fludarabine between 20 mg/m2/day and 900 mg/m2/day.
A method of enhancing an effector function of administered T cells in a patient in need of a T cell therapy comprising administering to the patient a dose of cyclophosphamide between 200 mg/m2/day and 2000 mg/m2/day and a dose of fludarabine between 20 mg/m2/day and 900 mg/m2/day.
A method of enhancing antigen presenting cell activation and/or availability in a patient in need of a T cell therapy comprising administering to the patient a dose of cyclophosphamide between 200 mg/m2/day and 2000 mg/m2/day and a dose of fludarabine between 20 mg/m2/day and 900 mg/m2/day.
A method of treating a patient having a lymphoma comprising administering daily to the patient about 500 mg/m2/day of cyclophosphamide and about 60 mg/m2/day of fludarabine for three days prior to administration of a therapeutically effective amount of engineered CAR T cells to the patient, wherein the engineered CAR T cells express a chimeric antigen receptor that binds to CD19 and further comprises a CD28 costimulatory domain and a CD3-zeta signaling region.
A method of treating a patient having a lymphoma comprising (i) administering to the patient about 500 mg/m2/day of cyclophosphamide and about 60 mg/m2/day of fludarabine and (ii) administering to the patient a therapeutically effective amount of engineered CAR T cells, wherein the engineered CAR T cells express a chimeric antigen receptor that binds to CD19 and further comprises a CD28 costimulatory domain and a CD3-zeta signaling region.
A method of treating a patient having a lymphoma comprising administering to the patient a therapeutically effective amount of engineered CAR T cells, wherein the patient has been conditioned by administration of about 500 mg/m2/day of cyclophosphamide and about 60 mg/m2/day of fludarabine and wherein the engineered CAR T cells express a chimeric antigen receptor that binds to CD19 and further comprises a CD28 costimulatory domain and a CD3-zeta signaling region.
A kit comprising (i) cyclophosphamide, (ii) fludarabine, and (iii) instructions to administer cyclophosphamide at a dose between 200 mg/m2/day and 2000 mg/m2/day and fludarabine at a dose between 20 mg/m2/day and 900 mg/m2/day daily for three days to a patient in need of an engineered CAR T cell therapy prior to the therapy.
A method of treating a patient having a lymphoma comprising administering daily to the patient about 200 mg/m2/day of cyclophosphamide and about 20 mg/m2/day of fludarabine for three days prior to administration of a therapeutically effective amount of engineered CAR T cells to the patient, wherein the engineered CAR T cells express a chimeric antigen receptor that binds to CD19 and further comprises a CD28 costimulatory domain and a CD3-zeta signaling region.
A method of conditioning a patient in need of a T cell therapy comprising administering to the patient a dose of cyclophosphamide between 1110 mg/m2/day and 2000 mg/m2/day and a dose of 25 mg/m2/day fludarabine, wherein the patient exhibits increased serum levels of IL-7, IL-15, IL-10, IL-5, IP-10, IL-8, MCP-1, PLGF, CRP, SICAM-1, sVCAM-1, or any combination thereof or decreased serum levels of perforin and/or MIP-1b after the administration of the cyclophosphamide and fludarabine.
A method of conditioning a patient in need of a T cell therapy comprising administering to the patient a dose of 1110 mg/m2/day cyclophosphamide and a dose of 25 mg/m2/day fludarabine.
A method of conditioning a patient in need of a T cell therapy comprising administering to the patient a dose of 200 mg/m2/day cyclophosphamide and a dose of 20 mg/m2/day fludarabine.
A method of conditioning a patient in need of a T cell therapy comprising administering to the patient a dose of 2000 mg/m2/day cyclophosphamide and a dose of 25 mg/m2/day fludarabine, wherein the patient exhibits increased serum levels of IL-7, IL-15, IL-10, IL-5, IP-10, IL-8, MCP-1, PLGF, CRP, SICAM-1, sVCAM-1, or any combination thereof or decreased serum levels of perforin and/or MIP-1b after the administration of the cyclophosphamide and fludarabine.
A method of conditioning a patient in need of a T cell therapy comprising administering to the patient a dose of 30 mg/kg/day cyclophosphamide and a dose of 25 mg/m2/day fludarabine.
Dependencies are inferred from the claim text.