Checkpoint inhibitor and a whole cell mycobacterium for use in cancer therapy
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.
1. In a method of treating, reducing, inhibiting or controlling a melanoma in a human patient by more than one intravenous administration of a therapeutically effective amount of a checkpoint inhibitor selected from the group consisting of an anti-PD-1 antibody, a human or humanized anti-PD-L1 antibody, and an anti-CTLA-4 antibody to the patient, the improvement comprising:
further administering intradermally to the human patient two or more doses of 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,
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, and
wherein the method results in enhanced therapeutic efficacy relative to administration of the checkpoint inhibitor alone.
2. The method of claim 1 , wherein the amount of the whole cell, heat-killed Mycobacterium obuense administered is from 10 7 to 10 9 cells per dose.
3. The method of claim 1 , wherein the two or more doses of the whole cell, heat-killed Mycobacterium obuense comprise three or more doses of the whole cell, heat-killed Mycobacterium obuense.
4. The method of claim 3 , wherein the three or more doses of the whole cell, heat-killed Mycobacterium obuense are administered over multiple weeks.
5. The method of claim 1 , wherein the improvement comprises administering the whole cell, heat-killed Mycobacterium obuense adjacent to the melanoma in the human patient.
6. The method of claim 1 , wherein the whole cell, heat-killed Mycobacterium obuense is administered before administration of the checkpoint inhibitor.
7. The method of claim 1 , wherein the whole cell, heat-killed Mycobacterium obuense is a rough variant.
8. The method of claim 1 , wherein the melanoma is metastatic.
9. The method of claim 1 , wherein enhanced therapeutic efficacy is measured by increased overall survival time.
10. The method of claim 1 , wherein enhanced therapeutic efficacy is measured by increased progression-free survival.
11. The method of claim 1 , wherein enhanced therapeutic efficacy is measured by a decrease or stabilization of melanoma tumor size.
12. The method of claim 1 , wherein enhanced therapeutic efficacy is measured by increased quality of life.
13. The method of claim 1 , wherein the checkpoint inhibitor is an anti-PD-1 antibody.
14. The method of claim 1 , wherein the checkpoint inhibitor is a human or humanized anti-PD-L1 antibody.
15. The method of claim 1 , wherein the checkpoint inhibitor is an anti-CTLA-4 antibody.
16. The method of claim 1 , wherein the melanoma is a primary neoplasia.