Method of reducing tumor relapse rate in immunotherapy by administration of lenzilumab
Inventors
DURRANT, Cameron • Chappell, Dale
Assignees
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Publication Number
US-10927168-B2
Publication Date
2021-02-23
Expiration Date
Abstract
Methods for reducing relapse rate or preventing occurrence of tumor relapse in a subject treated with immunotherapy, in an absence of an incidence of immunotherapy-related toxicity or in a presence of immunotherapy-related toxicity. Methods for reducing a level of a cytokine or chemokine other than GM-CSF in a subject having an incidence of immunotherapy-related toxicity, the methods comprising administering a recombinant GM-CSF antagonist to the subject. Methods for treating or preventing immunotherapy-related toxicity in a subject, the methods comprising administering to the subject chimeric antigen receptor-expressing T-cells (CAR-T cells), the CAR-T cells having a GM-CSF gene knockout (GM-CSFk/o CAR-T cells), and a recombinant hGM-CSF antagonist.
Core Innovation
The invention provides a method for reducing relapse rate or preventing occurrence of tumor relapse in a subject treated with immunotherapy. The method comprises administering to the subject a recombinant hGM-CSF antagonist, wherein the recombinant hGM-CSF antagonist is anti-hGM-CSF antibody lenzilumab. The disclosed anti-hGM-CSF antibody lenzilumab is characterized as an engineered human anti-hGM-CSF antibody with specific VL and VH framework and variable region combinations and sequence identity constraints.
The description includes requirements for CDR1, CDR2, CDR3, and FR4 regions, including constraints involving specific CDR and framework sequence elements and identity criteria for VH and V segment regions. The patent also states that lenzilumab binds to the same epitope as chimeric 19/2 and includes epitope competition relative to cl9/2.
The disclosure addresses GM-CSF antagonism in immunotherapy-related problem areas, including CAR-T contexts where GM-CSF blockade is discussed in relation to CRS and neurotoxicity. The patent discussion includes functional support for the antibody acting as a neutralizing antagonist and uses binding, competition, and neutralization potency concepts to support the intended effects.
Claims Coverage
The claim set centers on one independent claim directed to a relapse-reduction or prevention method in subjects receiving immunotherapy, with inventive features centered on administering the recombinant hGM-CSF antagonist lenzilumab. Dependent claims further refine the coverage by specifying immunotherapy context, relapse timing and quantitative performance constraints, and detailed antibody sequence and epitope constraints.
Recombinant hgm-csf antagonist as lenzilumab for relapse reduction or prevention
Administering to a subject treated with immunotherapy a recombinant hGM-CSF antagonist, wherein the recombinant hGM-CSF antagonist is anti-hGM-CSF antibody lenzilumab, to reduce relapse rate or prevent occurrence of tumor relapse.
Immunotherapy regimen types covered
The immunotherapy includes adoptive cell transfer, monoclonal antibody administration, cytokine administration, a cancer vaccine, T cell engaging therapies, or combinations of these.
Early relapse reduction performance constraint
Administering the recombinant GM-CSF antagonist reduces tumor relapse occurrence by 50% to 100% during the first one-quarter of a year compared with subjects treated with immunotherapy but not given the recombinant GM-CSF antagonist.
Relapse prevention duration window
Preventing tumor relapse from occurring within 12 to 36 months.
Lenzilumab vh/cdr/j/v identity and determinant constraints
Lenzilumab includes a VH region with a CDR3 binding specificity determinant RQRFPY (SEQ ID NO: 12), a J segment with at least 95% identity to human JH4 (SEQ ID NO: 14), and a V segment with at least 90% identity to a human germ line VHl 1-03 sequence.
Epitope equivalence to chimeric 19/2
Lenzilumab binds to the same epitope as chimeric 19/2.
Coverage centers on relapse rate reduction or prevention by administering recombinant hGM-CSF antagonist lenzilumab during immunotherapy, with additional refinements specifying covered immunotherapy types, quantified and timed relapse performance constraints, and structural constraints on lenzilumab sequence identity and epitope binding equivalence.
Stated Advantages
Reduces relapse rate or prevents occurrence of tumor relapse in a subject treated with immunotherapy.
Reduces tumor relapse occurrence by 50% to 100% during the first one-quarter of a year compared with subjects treated with immunotherapy but not given the recombinant GM-CSF antagonist.
Prevents tumor relapse from occurring within 12 to 36 months.
Documented Applications
Managing tumor relapse outcomes in subjects treated with immunotherapy using a recombinant hGM-CSF antagonist that is anti-hGM-CSF antibody lenzilumab.
Therapeutic use of anti-hGM-CSF antibodies, including lenzilumab, as hGM-CSF antagonists in the context of immunotherapy, including CAR-T contexts involving CRS and neurotoxicity, with discussion of GM-CSF blockade effects on CAR-T toxicity and efficacy.
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