Treatment of cancer by manipulation of commensal microflora

Patent metadata

Field	Value
Publication number	US-2016354416-A1
Application number	US-201615170284-A
Country	US
Kind code	A1
Filing date	Jun 1, 2016
Priority date	Jun 1, 2015
Publication date	Dec 8, 2016
Grant date	—

Abstract

Provided herein are methods of treatment and/or prevention of cancer by manipulation of commensal microflora. In particular, the amount, identity, presence, and/or ratio of microflora (e.g., gut microflora) in a subject is manipulated to facilitate one or more co-treatments.

First claim

We claim:

1 . A method of treating cancer in a human subject comprising administering to the subject an immune checkpoint inhibitor and a bacterial formulation comprising bacteria of the genera Bifidobacterium.

2 . The method of claim 1 , wherein at least 50% of the bacteria in the bacterial formulation are of the genera Bifidobacterium.

3 . The method of claim 1 , wherein at least 90% of the bacteria in the bacterial formulation are of the genera Bifidobacterium.

4 . The method of claim 1 , wherein the bacteria of the genus Bifidobacterium comprise bacteria of the species Bifidobacterium lactis, Bifidobacterium bifidium, Bifidobacterium longum, Bifidobacterium animalis, Bifidobacterium breve, Bifidobacterium infantis, Bifidobacterium catenulatum, Bifidobacterium pseudocatenulatum, Bifidobacterium adolescentis, Bifidobacterium angulatum, Bifidobacterium asteroides, Bifidobacterium boum, Bifidobacterium choerinum, Bifidobacterium coryneforme, Bifidobacterium cuniculi, Bifidobacterium denticolens, Bifidobacterium dentium, Bifidobacterium gallicum, Bifidobacterium gallinarum, Bifidobacterium indicum, Bifidobacterium inopinatum, Bifidobacterium magnum, Bifidobacterium merycicum, Bifidobacterium minimum, Bifidobacterium pseudolongum, Bifidobacterium pullorum, Bifidobacterium psychraerophilum, Bifidobacterium ruminantium, Bifidobacterium saeculare, Bifidobacterium scardovii, Bifidobacterium simiae, Bifidobacterium subtile, Bifidobacterium therammcidophilum, Bifidobacterium thermophilum, Bifidobacterium tsurumiense, Bifidobacterium urinalis or Bifidobacterium sp.

5 . The method of claim 1 , wherein the bacterial formulation is administered by oral administration or rectal administration.

6 . The method of claim 5 , wherein the bacterial formulation is administered by oral administration.

7 . The method of claim 1 , wherein the bacterial formulation comprises at least 5×10 6 CFU of bacteria of the genera Bifidobacterium.

8 . The method of claim 1 , wherein the bacterial formulation is administered to the subject in two or more doses.

9 . The method of claim 9 , wherein the administration of the two or more doses are separated by at least 1 week.

10 . The method of claim 1 , further comprising administering to the subject an antibiotic prior to the administration of the bacterial formulation.

11 . The method of claim 10 , wherein the antibiotic is administered to the subject at least 1 day before the bacterial formulation is administered to the subject.

12 . The method of claim 1 , wherein the immune checkpoint inhibitor is a protein or polypeptide that binds to an immune checkpoint protein.

13 . The method of claim 12 , wherein the immune checkpoint protein is CTLA4, PD-1, PD-L1, PD-L2, A2AR, B7-H3, B7-H4, BTLA, KIR, LAG3, TIM-3 or VISTA.

14 . The method of claim 13 , wherein the immune checkpoint protein is PD-1 or PD-L1.

15 . The method of claim 1 , wherein the immune checkpoint inhibitor is an antibody or antigen binding fragment thereof that binds to an immune checkpoint protein.

16 . The method of claim 15 , wherein the immune checkpoint protein is CTLA4, PD-1, PD-L1, PD-L2, A2AR, B7-H3, B7-H4, BTLA, KIR, LAG3, TIM-3 or VISTA.

17 . The method of claim 16 , wherein the immune checkpoint protein is PD-1 or PD-L1.

18 . The method of claim 1 , wherein the immune checkpoint inhibitor is nivolumab, pembrolizumab, pidilizumab, AMP-224, AMP-514, STI-A1110, TSR-042, RG-7446, BMS-936559, BMS-936558, MK-3475, CT O11, MPDL3280A, MEDI-4736, MSB-0020718C, AUR-012 and STI-A1010.

19 . The method of claim 1 , wherein the immune checkpoint inhibitor is administered by intravenous injection, intramuscular injection, intratumoral injection or subcutaneous injection.

20 . A method of treating cancer in a human subject comprising administering to the subject a bacterial formulation comprising at least 5×10 6 CFU of bacteria of the genera Bifidobacterium , wherein at least 50% of the bacteria in the bacterial formulation are of the genera Bifidobacterium.

21 . The method of claim 20 , wherein at least 90% of the bacteria in the bacterial formulation are of the genera Bifidobacterium.

22 . The method of claim 20 , wherein the bacteria of the genus Bifidobacterium comprise bacteria of the species Bifidobacterium lactis, Bifidobacterium bifidium, Bifidobacterium longum, Bifidobacterium animalis, Bifidobacterium breve, Bifidobacterium infantis, Bifidobacterium catenulatum, Bifidobacterium pseudocatenulatum, Bifidobacterium adolescentis, Bifidobacterium angulatum, Bifidobacterium asteroides, Bifidobacterium boum, Bifidobacterium choerinum, Bifidobacterium coryneforme, Bifidobacterium cuniculi, Bifidobacterium denticolens, Bifidobacterium dentium, Bifidobacterium gallicum, Bifidobacterium gallinarum, Bifidobacterium indicum, Bifidobacterium inopinatum, Bifidobacterium magnum, Bifidobacterium merycicum, Bifidobacterium minimum, Bifidobacterium pseudolongum, Bifidobacterium pullorum, Bifidobacterium psychraerophilum, Bifidobacterium ruminantium, Bifidobacterium saeculare, Bifidobacterium scardovii, Bifidobacterium simiae, Bifidobacterium subtile, Bifidobacterium therammcidophilum, Bifidobacterium thermophilum, Bifidobacterium tsurumiense, Bifidobacterium urinalis or Bifidobacterium sp.

23 . The method of claim 20 , wherein the bacterial formulation is administered by oral administration or rectal administration.

24 . The method of claim 23 , wherein the bacterial formulation is administered by oral administration.

25 . The method of claim 20 , wherein the bacterial formulation is administered to the subject in two or more doses.

26 . The method of claim 20 , further comprising administering to the subject an antibiotic before the bacterial formulation is administered to the subject.

27 . The method of claim 20 , further comprising administering to the subject an immune checkpoint inhibitor.

28 . The method of claim 27 , wherein the immune checkpoint inhibitor is an antibody or antigen binding fragment thereof that binds to CTLA4, PD-1, PD-L1, PD-L2, A2AR, B7-H3, B7-H4, BTLA, KIR, LAG3, TIM-3 or VISTA.

29 . The method of claim 27 , wherein the immune checkpoint inhibitor is an antibody or antigen binding fragment thereof that binds to PD-1 or PD-L1.

30 . The method of claim 27 , wherein the immune checkpoint inhibitor is nivolumab, pembrolizumab, pidilizumab, AMP-224, AMP-514, STI-A1110, TSR-042, RG-7446, BMS-936559, BMS-936558, MK-3475, CT O11, MPDL3280A, MEDI-4736, MSB-0020718C, AUR-012 and STI-A1010.

Assignees

• Univ Chicago

Inventors

• Gajewski Thomas F
• Sivan Ayelet
• Corrales Leticia

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P31/04

  Antibacterial agents · CPC title

• A61P35/02

  specific for leukemia · CPC title

• C07K16/2827

  against B7 molecules, e.g. CD80, CD86 · CPC title