Methods of treating immunotherapy-related toxicity using a GM-CSF antagonist
Inventors
DURRANT, Cameron • Chappell, Dale
Assignees
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Publication Number
US-10870703-B2
Publication Date
2020-12-22
Expiration Date
Abstract
Methods of inhibiting or reducing the incidence or the severity of immunotherapy-related toxicity in a subject, the method comprising a step of administering a recombinant hGM-CSF antagonist to the subject, wherein said administering inhibits or reduces the incidence or the severity of immunotherapy-related toxicity in said subject, are provided. An hGM-CSF antagonist for use in methods of inhibiting or reducing the incidence or the severity of immunotherapy-related toxicity in a subject also are provided.
Core Innovation
The invention relates to administering a recombinant hGM-CSF antagonist to a subject treated with CAR-T cell therapy, specifically an anti-hGM-CSF antibody lenzilumab, to treat cytokine release syndrome (CRS) and related toxicities by neutralizing hGM-CSF in the subject. It characterizes CRS and cytokine storm as a clinical problem associated with CAR-T cell therapy and focuses on therapeutic treatment and prevention through hGM-CSF neutralization.
The invention further addresses CAR-T related neurotoxicity by administering recombinant hGM-CSF antagonist lenzilumab to neutralize hGM-CSF in the subject. It states that administering lenzilumab inhibits or reduces the incidence or severity of CAR-T related toxicity, including CRS and neurotoxicity, and emphasizes reducing CRS/neuroinflammation while preserving CAR-T efficacy and expansion.
The document describes antibody engineering and binding and neutralization characterization for anti-hGM-CSF antibodies, including lenzilumab, with measurements such as Fab binding and surface plasmon resonance (SPR/Biacore), and neutralization assays. It also links GM-CSF blockade to mitigation of CAR-T related CRS/neurotoxicity and includes preclinical and clinical-supporting content, including MRI T2 FLAIR neuroinflammation reduction and a stated clinical safety profile in more than 100 patients.
Claims Coverage
The partial content identifies three independent claims. Together, they cover treating CRS in a subject receiving CAR-T cell therapy, inhibiting or reducing the incidence or severity of CAR-T related toxicity including CRS and neurotoxicity, and treating CAR-T cell related neurotoxicity, each via administration of recombinant hGM-CSF antagonist lenzilumab with hGM-CSF neutralization.
Recombinant hgm-csf antagonist lenzilumab for CRS treatment during CAR-T therapy
A method treating cytokine release syndrome (CRS) in a subject treated with CAR-T cell therapy, comprising administering a recombinant hGM-CSF antagonist wherein the recombinant hGM-CSF antagonist is anti-hGM-CSF antibody lenzilumab and wherein said administering neutralizes hGM-CSF in said subject.
Recombinant hgm-csf antagonist lenzilumab for inhibiting CAR-T related toxicity
A method of inhibiting or reducing the incidence or the severity of CAR-T related toxicity in a subject, comprising administering a recombinant hGM-CSF antagonist wherein the recombinant hGM-CSF antagonist is anti-hGM-CSF antibody lenzilumab and wherein said administering inhibits or reduces the incidence or the severity of CAR-T related toxicity in said subject.
Recombinant hgm-csf antagonist lenzilumab for CAR-T related neurotoxicity
A method of treating CAR-T cell related neurotoxicity in a subject treated with CAR-T cell therapy, comprising administering a recombinant hGM-CSF antagonist wherein the recombinant hGM-CSF antagonist is anti-hGM-CSF antibody lenzilumab and wherein said administering neutralizes hGM-CSF in said subject.
Across the independent claims, the central inventive theme is co-administering lenzilumab, an anti-hGM-CSF antibody, as a recombinant hGM-CSF antagonist to neutralize hGM-CSF, thereby treating CRS and CAR-T related neurotoxicity and inhibiting or reducing the incidence or severity of CAR-T related toxicity.
Stated Advantages
Reduces immunotherapy-related toxicities, including cytokine release syndrome (CRS) and CAR-T related neurotoxicity/CRES.
Reduces inflammatory factors, including circulating GM-CSF and other cytokines or biomarkers.
Does not reduce CAR-T immunotherapy efficacy.
Potentially increases CAR-T expansion.
Reduces incidence or severity of CAR-T related toxicity.
Neutralizes hGM-CSF in the subject.
Treats cytokine release syndrome (CRS) occurring in a subject treated with CAR-T cell therapy.
Treats CAR-T cell related neurotoxicity.
Reduces CAR-T related neurotoxicity by about 90%.
Preserves CAR-T efficacy and expansion.
Documented Applications
Treating cytokine release syndrome (CRS) in a subject treated with CAR-T cell therapy by administering recombinant hGM-CSF antagonist lenzilumab.
Inhibiting or reducing the incidence or severity of CAR-T related toxicity in a subject by administering recombinant hGM-CSF antagonist lenzilumab.
Treating CAR-T cell related neurotoxicity in a subject treated with CAR-T cell therapy by administering recombinant hGM-CSF antagonist lenzilumab.
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