Checkpoint inhibitor and a whole cell Mycobacterium for use in cancer therapy
Inventors
AKLE, CHARLES • Grange, John • Bilyard, Kevin
Assignees
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Publication Number
US-11000584-B2
Publication Date
2021-05-11
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, simultaneously, separately or sequentially with administration of the immunomodulator. The immunomodulator preferably comprises a whole cell Mycobacterium, for example, M. vaccae or M. obuense.
Core Innovation
The invention relates to combination cancer immunotherapy in a human patient with colorectal neoplasia by using a checkpoint inhibitor selected from anti-PD-1 antibody, human or humanized anti-PD-L1 antibody, an anti-CTLA-4 antibody, or combinations thereof. The method includes intravenous administration of multiple doses of the checkpoint inhibitor to achieve a therapeutically effective amount.
The improvement includes further administering two or more doses of whole cell, heat-killed Mycobacterium obuense to the human patient. Each dose of whole cell, heat-killed Mycobacterium obuense is administered in an amount of 0.1 mg to 1 mg per dose.
The whole cell, heat-killed Mycobacterium obuense is administered simultaneously, separately or sequentially with respect to the checkpoint inhibitor, with each being administered on multiple days. The method is described as resulting in enhanced therapeutic efficacy relative to administration of the checkpoint inhibitor alone.
In the described example context, the combination is associated with greater tumor-size reduction compared with checkpoint inhibitor alone and with heat-killed Mycobacterium obuense alone, including references to overall survival, progression-free survival, response rate, and reduction of metastatic disease as measurable clinical endpoints.
Claims Coverage
The independent claim identified is clm-00001, which specifies a colorectal neoplasia treatment method using multi-day intravenous checkpoint inhibitor dosing combined with two or more doses of whole cell, heat-killed Mycobacterium obuense, including a per-dose mass range and a timing relationship across the checkpoint inhibitor administration.
Multi-dose intravenous checkpoint inhibitor therapy with combination improvement
Administering a therapeutically effective amount of a checkpoint inhibitor selected from anti-PD-1 antibody, human or humanized anti-PD-L1 antibody, anti-CTLA-4 antibody, or combinations thereof by more than one intravenous administration, and providing an improvement comprising further administration of whole cell, heat-killed Mycobacterium obuense.
Further administering two or more doses of whole cell, heat-killed Mycobacterium obuense
Further administering to the human patient two or more doses of whole cell, heat-killed Mycobacterium obuense.
Per-dose mass range for whole cell, heat-killed Mycobacterium obuense
Wherein 0.1 mg to 1 mg of the whole cell, heat-killed Mycobacterium obuense is administered to the human patient per dose.
Simultaneous, separate, or sequential timing with multi-day checkpoint inhibitor dosing
Wherein the whole cell, heat-killed Mycobacterium obuense is administered simultaneously, separately or sequentially with respect to the checkpoint inhibitor, with each of the whole cell, heat-killed Mycobacterium obuense and checkpoint inhibitor being administered on multiple days.
Enhanced therapeutic efficacy relative to checkpoint inhibitor alone
Wherein the method results in enhanced therapeutic efficacy relative to administration of the checkpoint inhibitor alone.
Across the independent claim, the main inventive features are the multi-dose intravenous checkpoint inhibitor regimen for colorectal neoplasia combined with two or more doses of whole cell, heat-killed Mycobacterium obuense, administered at 0.1 mg to 1 mg per dose and given simultaneously, separately, or sequentially relative to the checkpoint inhibitor over multiple days, producing enhanced therapeutic efficacy compared with checkpoint inhibitor alone.
Stated Advantages
Enhanced therapeutic efficacy relative to administration of the checkpoint inhibitor alone.
Documented Applications
Treating, reducing, inhibiting or controlling colorectal neoplasia in a human patient using a combination of a checkpoint inhibitor and whole cell, heat-killed Mycobacterium obuense with enhanced therapeutic efficacy.
A described example context includes a xenograft model of pancreatic cancer showing greater tumor-size reduction with the combination versus checkpoint inhibitor alone and versus heat-killed Mycobacterium obuense alone.
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