Checkpoint inhibitor and a whole cell Mycobacterium for use in cancer therapy
Inventors
AKLE, CHARLES • Brunet, Laura Rosa
Assignees
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Publication Number
US-11207405-B2
Publication Date
2021-12-28
Expiration Date
Abstract
An immunomodulator for use in the treatment, reduction, inhibition or control of a neoplastic disease in a patient intended to undergo checkpoint inhibition therapy, selected from a cell, protein, peptide, antibody or antigen binding fragment thereof, directed against CTLA-4, PD-1, PD-L1 and combinations thereof, simultaneously, separately or sequentially with administration of the immunomodulator. The immunomodulator comprises a whole cell Mycobacterium, for example, M. vaccae or M. obuense.
Core Innovation
The invention relates to cancer therapy in a subject using a combination of a checkpoint inhibitor and an immunomodulator, where the method results in enhanced therapeutic efficacy relative to administration of the checkpoint inhibitor or immunomodulator alone. The checkpoint inhibitor comprises a human or humanized antibody directed against PD-L1, a human or humanized antibody directed against PD-1, or a combination thereof, and the immunomodulator comprises whole cell, non-pathogenic heat-killed Mycobacterium obuense.
The immunomodulator consisting of whole cell, non-pathogenic heat-killed Mycobacterium obuense is administered to the subject prior to administering the checkpoint inhibitor. The approach is framed for treating, reducing, inhibiting, or controlling a neoplasia, tumour, or cancer, with the combination producing enhanced therapeutic efficacy versus each agent alone.
The document further discusses preferred checkpoint targets and includes examples emphasizing synergy and measurable clinical and immunological endpoints in cancer models. In particular, the combination is associated with tumour control and immune cell infiltration measured by markers including CD3+CD8+ cells and FoxP3+ Treg cells, as well as clinical endpoints such as overall survival time.
Claims Coverage
The partial content provides one independent claim and dependent refinements that specify the timing of administration and the checkpoint antibody target(s), with further features including selected checkpoint antibodies, biomarker-based patient selection, quantitative constraints for the immunomodulator, and specific efficacy endpoints.
Pd-1/pd-l1 checkpoint antibody combination with heat-killed mycobacterium obuense
A method of treating, reducing, inhibiting or controlling a neoplasia, tumour or cancer in a subject comprising administering a checkpoint inhibitor comprising a human or humanized antibody directed against PD-L1, a human or humanized antibody directed against PD-1, or a combination thereof, and an immunomodulator wherein the immunomodulator comprises whole cell, non-pathogenic heat-killed Mycobacterium obuense, and wherein the method results in enhanced therapeutic efficacy relative to administration of the checkpoint inhibitor or immunomodulator alone.
Immunomodulator prior to checkpoint inhibitor
The method wherein the whole cell, non-pathogenic heat-killed Mycobacterium obuense is administered to the subject prior to administering the checkpoint inhibitor.
Across the independent claim and its dependent refinements, the central claimed concept is an anti-PD-1/anti-PD-L1 checkpoint inhibitor regimen combined with whole cell, non-pathogenic heat-killed Mycobacterium obuense as an immunomodulator, with enhanced therapeutic efficacy and a stated ordering where the immunomodulator is administered prior to the checkpoint inhibitor.
Stated Advantages
Enhanced therapeutic efficacy relative to administration of the checkpoint inhibitor or immunomodulator alone.
Potential to reduce toxicity is mentioned as a potential outcome.
Documented Applications
Treating, reducing, inhibiting or controlling a neoplasia, tumour or cancer in a subject.
Mouse model applications are described, including a xenograft pancreatic cancer model with tumour size/control and immune cell infiltration measurements using FACS markers such as CD3+CD8+ cells and FoxP3+ Treg cells.
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