Checkpoint inhibitor and a whole cell
An immunomodulator is 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 includes a whole cell Mycobacterium , such as 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 a human or humanized anti-PD-L1 antibody to the human 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 human or humanized anti-PD-L1 antibody, with each of the whole cell, heat-killed Mycobacterium obuense and human or humanized anti-PD-L1 antibody being administered on multiple days, and
wherein the method results in enhanced therapeutic efficacy relative to administration of the human or humanized anti-PD-L1 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 improvement comprises intradermally administering the whole cell, heat-killed Mycobacterium obuense adjacent to the pancreatic neoplasia in the human patient.
6. The method of claim 1 , wherein the whole cell, heat-killed Mycobacterium obuense is administered before administration of the human or humanized anti-PD-L1 antibody.
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 pancreatic neoplasia is a metastatic pancreatic neoplasia.
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 pancreatic neoplasia 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 pancreatic neoplasia is a primary pancreatic neoplasia.