US20190292246A1 – September 26, 2019 – COMBINATION THERAPY OF A CELL BASED THERAPY AND A MICROGLIA IMHIBITOR

Please complete the required fields.




Inventors :

Hyam I. LEVITSKY

Owner :

JUNO THERAPEUTICS, INC.

Application Number :

US16345214

Document Number :

US20190292246A1

Priority Date :

November 3, 2017

Filing Date :

November 3, 2017

Date of Grant/ Publication :

September 26, 2019

Class :

C07K16 / 18; A61K31 / 444; A61K31 / 675; A61K9 / 00; A61K35 / 17

Abstract

Provided are methods, kits and compositions for ameliorating toxicity, such as cytokine release syndrome or neurotoxicity, suspected or being induced by or associated with, administration of a therapeutic agent, such as a immunotherapeutic agent targeting T cells and/or genetically engineered T cells, e.g. chimeric antigen receptor (CAR)-expressing T cells. The methods involve administering an additional agent, such as an agent having anti-oxidant or anti-inflammatory properties, that modulates immune cells such as by preventing or reducing the production of pro-inflammatory cytokines or stress cytokines and/or promoting differentiation to a neuroprotective phenotype, and/or capable of preventing, blocking or reducing microglial cell activation or function and/or capable of modulating, such as promoting, the activity of NRF2 or a component of an NRF2-regulated pathway, and/or one or more components involved in an antioxidant response element (ARE). The provided methods can be used in connection with or for methods of treating a disease or condition.

Claim(s)

1 . A method of treatment, comprising administering to a subject having a disease or condition a therapeutic agent for treating a disease or condition, wherein: administration of the therapeutic agent is or is suspected of being associated with a risk of eliciting a toxic outcome or symptom; and the subject has been administered, prior to initiation of the therapy, (a) an agent capable of preventing, blocking or reducing or altering an activity or function or phenotype of a microglial cell activity or function or (b) an agent capable of modulating an NRF2 or KEAP1 or HCAR2 or (c) an agent that is an ester of a fumaric acid.;
4 . A method of treatment, comprising: (a) administering to a subject (a) an agent capable of preventing, blocking or reducing or altering an activity or function or phenotype of a microglial cell activity or function or (b) an agent capable of modulating an NRF2 or KEAP1 or HCAR2 or (c) an agent that is an ester of a fumaric acid; and (b) after the administration in (a), administering to the subject having a disease or condition a therapeutic agent for treating a disease or condition, wherein administration of the therapeutic agent is or is suspected of being associated with a risk of eliciting a toxic outcome or symptom.;
15 . A method of treatment, comprising: (a) administering to a subject having a disease or condition a therapeutic agent for treating a disease or condition, wherein administration of the therapeutic agent is or is suspected of being associated with a risk of eliciting a toxic outcome or symptom of or related to severe CRS or severe neurotoxicity in the subject and/or grade 2 or grade 3 or higher CRS or grade 2 or grade 3 or higher neurotoxicity in the subject; and (b) administering to the subject (a) an agent capable of preventing, blocking or reducing or altering an activity or function or phenotype of a microglial cell activity or function or (b) an agent capable of modulating an NRF2 or KEAP1 or HCAR2 or (c) an agent that is an ester of a fumaric acid, wherein the agent is administered (i) at a time that is within or within about 1 day, 2 days, 3 days, four days, five days, six days or seven days after administration of the therapeutic agent and/or (ii) at or about or within 24 hours of the subject exhibiting a first sign or symptom indicative of CRS or neurotoxicity after administration of the therapy.;
18 . A method of treatment, comprising: (a) administering to a subject having a disease or condition a therapeutic agent for treating a disease or condition, wherein the therapeutic agent is or is suspected of being associated with a risk of eliciting a toxic outcome or symptom; and (b) administering to the subject an agent capable of preventing, blocking or reducing or altering an activity or function or phenotype of a microglial cell activity or function or (b) an agent capable of modulating an NRF2 or KEAP1 or HCAR2 or (c) an agent that is an ester of a fumaric acid, wherein the agent is administered at or about or within 24 hours of the subject exhibiting a fever after administration of the therapeutic agent.;
30 . A method of ameliorating toxicity induced by or associated with administration of a therapeutic agent, the method comprising: (a) administering to a subject having a disease or condition a therapeutic agent for treating a disease or condition, wherein the therapeutic agent is or is suspected of being associated with a risk of eliciting a toxic outcome or symptom; and (b) administering to the subject an agent capable of preventing, blocking or reducing or altering an activity or function or phenotype of a microglial cell activity or function or (b) an agent capable of modulating an NRF2 or KEAP1 or HCAR2 or (c) an agent that is an ester of a fumaric acid, wherein the agent is administered in a dosage regimen until the risk or suspected risk of a toxic outcome or symptom associated with administration of the therapeutic agent has subsided or is not present.;
68 . A method of treatment, comprising administering, to a subject having a disease or condition, a cell therapy for treating a disease or condition, wherein the cell therapy comprises cells that secrete an inhibitor of colony-stimulating factor-1 receptor (CSF1R).;
131 . A combination, comprising: a first composition comprising genetically engineered cells expressing a recombinant receptor that specifically binds to an antigen; ad a second composition comprising an inhibitor of colony stimulating factor 1 receptor (CSF1R).;
151 . An article of manufacture, comprising: (a) a pharmaceutical composition comprising engineered immune cells and/or a T cell-engaging therapy; and (b) instructions for administration of the composition to a subject having a disease or condition, in combination with an agent capable of reducing or preventing or blocking activation or function of microglial cells in the subject.;
152 . An article of manufacture, comprising: (a) a pharmaceutical composition comprising an agent capable of reducing or preventing or blocking activation or function of microglial cells; and (b) instructions for administration of the composition to a subject having a disease or condition, in combination with an agent for treating said disease or condition, which agent comprises an engineered immune cell and/or T cell-engaging therapy.

Summary

No Comments

Leave a comment

Sorry, you must be logged in to post a comment. Login