Checkpoint inhibitor and a whole cell
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 pancreatic neoplasia in a human patient by more than one intravenous administration of a therapeutically effective amount of an anti-CTLA-4 antibody and/or anti-PD-1 antibody to the human patient, the improvement comprising:
further administering 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 anti-CTLA-4 antibody and/or anti-PD-1 antibody, with each of the whole cell, heat-killed Mycobacterium obuense and anti-CTLA-4 antibody and/or anti-PD-1 antibody being administered on multiple days, and
wherein the method results in enhanced therapeutic efficacy relative to administration of the anti-CTLA-4 antibody and/or anti-PD-1 antibody 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 whole cell, heat-killed Mycobacterium obuense is administered before administration of the anti-CTLA-4 antibody and/or anti-PD-1 antibody.
6. The method of claim 1 , wherein the anti-CTLA-4 antibody and/or anti-PD-1 antibodies are administered in combination to the human patient.
7. The method of claim 1 , further comprising the administration of a human or humanized anti-PD-L1 antibody.
8. The method of claim 6 , further comprising the administration of a human or humanized anti-PD-L1 antibody.
9. The method of claim 1 , wherein the whole cell, heat-killed Mycobacterium obuense is a rough variant.
10. The method of claim 1 , wherein the pancreatic neoplasia is a metastatic pancreatic neoplasia.
11. The method of claim 1 , wherein enhanced therapeutic efficacy is measured by increased overall survival time.
12. The method of claim 1 , wherein enhanced therapeutic efficacy is measured by increased progression-free survival.
13. The method of claim 1 , wherein enhanced therapeutic efficacy is measured by a decrease or stabilization of pancreatic neoplasia size.
14. The method of claim 1 , wherein enhanced therapeutic efficacy is measured by increased quality of life.
15. The method of claim 1 , wherein the pancreatic neoplasia is a primary pancreatic neoplasia.
16. The method of claim 1 , wherein the Mycobacterium obuense is administered via the parenteral, oral, sublingual, nasal or pulmonary route.
17. The method of claim 1 , wherein the Mycobacterium obuense is administered via a parenteral route selected from subcutaneous, intradermal, subdermal, intraperitoneal, or intravenous.
18. The method of claim 1 , wherein the Mycobacterium obuense is administered intradermally.
19. The method of claim 1 , wherein the intravenous administration comprises intravenous administration of the anti-CTLA-4 antibody to the human patient.
20. The method of claim 1 , wherein the intravenous administration comprises intravenous administration of the anti-PD-1 antibody to the human patient.