Replacement of Cytotoxic Preconditioning Before Cellular Immunotherapy

Abstract

Provided herein are therapeutic compositions and methods that keep cellular immunotherapies in the circulation or at the site of injection for extended periods of time without resorting to the use of cytotoxic preconditioning. For example, the compositions and methods herein lymphodeplete and reduce or ablate sites in the secondary lymphatics where the cellular immunotherapy is bound and sequestered, without the use of cytotoxic preconditioning.

1 - 23 . (canceled) 
     
     
         24 . A method of enhancing adoptive cellular therapy (ACT) in a patient suffering from an autoimmune disease or an infectious disease, the method comprising:
 administering to the patient dexamethasone or another glucocorticoid at a dose that is effective to cause substantial lymphodepletion and/or cause ablation of secondary lymphatic germinal centers,   wherein the method does not include the administration of a chemotherapeutic agent for a duration of more than 1 day; and   wherein the dose of dexamethasone or another glucocorticoid that is effective to cause lymphodepletion and/or cause ablation of secondary lymphatic germinal centers a human equivalent dose (HED) of at least 3 mg/kg dexamethasone or a dose of another glucocorticoid that is equivalent to at least 3 mg/kg dexamethasone.   
     
     
         25 . The method of  claim 24 , wherein the ACT comprises either a cell used to enhance the immune system in treating a disease in said patient or a cell derived from an immune lineage which directly treats said disease. 
     
     
         26 . The method of  claim 24 , wherein the dexamethasone or another glucocorticoid is selected from the group consisting of dexamethasone, dexamethasone base, prednisone, methylprednisolone, and a dexamethasone analogue. 
     
     
         27 . The method of  claim 24 , wherein the dexamethasone or another glucocorticoid is dexamethasone. 
     
     
         28 . The method of  claim 24 , wherein the dose of dexamethasone or another glucocorticoid that is effective to cause lymphodepletion and/or cause ablation of secondary lymphatic germinal centers is a human equivalent dose (HED) of at least about 4 mg/kg, at least about 5 mg/kg, at least about 6 mg/kg, at least about 7 mg/kg, at least about 8 mg/kg, at least about 9 mg/kg, at least about 10 mg/kg, at least about 11 mg/kg, or at least about 12 mg/kg of dexamethasone or a dose of another glucocorticoid that is equivalent to at least about 4 mg/kg, at least about 5 mg/kg, at least about 6 mg/kg, at least about 7 mg/kg, at least about 8 mg/kg, at least about 9 mg/kg, at least about 10 mg/kg, at least about 11 mg/kg, or at least about 12 mg/kg human equivalent dose (HED) of dexamethasone. 
     
     
         29 . The method of  claim 24 , wherein the dose of dexamethasone or another glucocorticoid that is effective to cause lymphodepletion and/or cause ablation of secondary lymphatic germinal centers is a human equivalent dose (HED) of up to about 26 mg/kg dexamethasone or a dose of another glucocorticoid that is equivalent to up to about 26 mg/kg human equivalent dose (HED) of dexamethasone. 
     
     
         30 . The method of  claim 24 , wherein the dose of dexamethasone or another glucocorticoid that is effective to cause lymphodepletion and/or cause ablation of secondary lymphatic germinal centers is a human equivalent dose (HED) of between about 9 mg/kg to about 12 mg/kg of dexamethasone, or a dose of another glucocorticoid that is equivalent to between about 9 mg/kg to about 12 mg/kg. 
     
     
         31 . The method of  claim 24 , wherein the dose of dexamethasone or another glucocorticoid that is effective to cause lymphodepletion and/or cause ablation of secondary lymphatic germinal centers is between 5-26 mg/kg human equivalent dose (HED) of dexamethasone or a dose of another glucocorticoid that is equivalent to between 5-26 mg/kg human equivalent dose (HED) of dexamethasone. 
     
     
         32 . The method of  claim 24 , wherein the patient is a human. 
     
     
         33 . The method of  claim 24 , wherein the enhanced ACT comprises reduced autoimmune causing cell count in a patient with an autoimmune disease, or reduced infectious agent load in a patient with an infectious disease. 
     
     
         34 . The method of  claim 24 , wherein the dexamethasone or another glucocorticoid is administered before ACT commences. 
     
     
         35 . The method of  claim 24 , wherein the dexamethasone or another glucocorticoid is administered at least 12 hours before ACT commences. 
     
     
         36 . The method of  claim 24 , wherein the dexamethasone or another glucocorticoid is administered at one or more time points between about 72 to about 12 hours prior to commencement of ACT. 
     
     
         37 . The method of  claim 24 , wherein the ACT comprises administration of T cells. 
     
     
         38 . The method of  claim 24 , wherein no chemotherapeutic agents are administered to the patient. 
     
     
         39 . A method of performing adoptive cellular therapy (ACT) in a patient suffering from an autoimmune disease or an infectious disease, said method comprising:
 administering to the patient dexamethasone or another glucocorticoid at a dose that is effective to cause substantial lymphodepletion and/or cause ablation of secondary lymphatic germinal centers; and   administering ACT to the patient;   wherein the method does not include the administration of a chemotherapeutic agent for a duration of more than 1 day or more; and   wherein the dose of dexamethasone or another glucocorticoid that is effective to cause lymphodepletion and/or cause ablation of secondary lymphatic germinal centers a human equivalent dose (HED) of at least 3 mg/kg dexamethasone or a dose of another glucocorticoid that is equivalent to at least 3 mg/kg dexamethasone.   
     
     
         40 . The method of  claim 39 , wherein the ACT comprises either a cell used to enhance the immune system in treating a disease in said patient or a cell derived from an immune lineage which directly treats said disease. 
     
     
         41 . The method of  claim 39 , wherein the dose of dexamethasone or another glucocorticoid that is effective to cause lymphodepletion and/or cause ablation of secondary lymphatic germinal centers is between 5-26 mg/kg human equivalent dose (HED) of dexamethasone or a dose of another glucocorticoid that is equivalent to between 5-26 mg/kg human equivalent dose (HED) of dexamethasone. 
     
     
         42 . The method of  claim 39 , wherein the patient is a human. 
     
     
         43 . The method of  claim 39 , wherein the dexamethasone or another glucocorticoid is administered before ACT commences.