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.
Claims12
A method of treating a patient having a tumor comprising (i) administering to the patient a single dose of cyclophosphamide at about 900 mg/m2/day and one or more doses of fludarabine at about 25 mg/m2/day;
- and (ii) administering to the patient a therapeutically effective amount of engineered chimeric antigen receptor (CAR) T cells, wherein the patient is determined to have an increase in the serum levels of IL-15 of at least 5-fold, IL-7 of at least 2-fold, and an increase in at least one of MCP-1 or CRP of at least 1.5 fold or IP-10 of at least 2-fold on the day of but prior to administration of the CAR-T cells, after the administration of cyclophosphamide and fludarabine;
- wherein the tumor is a leukemia and the engineered CAR-T cells are anti-CD19 CAR-T cells.
The method of 1, wherein the patient after the administration of cyclophosphamide and fludarabine and/or the T cell therapy further exhibits an increased serum concentration of a cytokine or a pro-inflammatory factor selected from the group consisting of IL-10, IL-5, IL-8, PLGF, SICAM-1, sVCAM-1, IL-1, IL-2, IL-3, IL-4, IL-6, IL-9, IL-11, IL-12, IL-13, IL-14, IL-15, IL-16, IL-17, IL-20, granulocyte macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), vascular endothelial growth factor D (VEGF-D), macrophage inflammatory protein 1β (MIP-1β), leukemia inhibitory factor (LIF), oncostatin M (OSM), interferon (IFN) alpha, IFN-beta, IFN-gamma, tumor necrosis factor (TNF) alpha, TNF-beta, CD154, lymphotoxin (LT) beta, 4-1BB ligand (4-1BBL), a proliferation-inducing ligand (APRIL), CD70, CD153, CD178, glucocorticoid-induced TNFR-related ligand (GITRL), tumor necrosis factor superfamily member 14 (TNFSF14), OX40L, TNF-αnd ApoL-related leukocyte-expressed ligand 1 (TALL-1), TNF-related apoptosis-inducing ligand (TRAIL), chemokine (C-C motif) ligand (CCL) 1, macrophage inflammatory protein 1 alpha (MIP-1a or CCL3), CCL5, monocyte-specific chemokine 3 (MCP3 or CCL7), monocyte chemoattractant protein 2 (MCP-2 or CCL8), CCL13, thymus and activation regulated chemokine (TARC or CCL17), CCL22, and any combination thereof.
Dependencies are inferred from the claim text.