Microbiota composition, as a marker of responsiveness to anti-PD1/PD-L1/PD-L2 antibodies and use of microbial modulators for improving the efficacy of an anti-PD1/PD-L1/PD-L2 AB-based treatment

Patent metadata

Field	Value
Publication number	US-12144839-B2
Application number	US-202318300049-A
Country	US
Kind code	B2
Filing date	Apr 13, 2023
Priority date	Dec 22, 2016
Publication date	Nov 19, 2024
Grant date	Nov 19, 2024

Abstract

The invention relates to gut microbiota profiles associated with response or resistance to treatments with ICB, in particular with anti-PD1 or anti PD-L1 or anti-PD-L2 antibodies. In particular, the invention pertains to a theranostic method for identifying good responders, to whom an anti-PD1 or anti PD-L1 or anti-PD-L2 can be administered, while a pre-treatment based on FMT and/or immunogenic probiotics is recommended to bad responders exhibiting a dysbiosis. In particular, the present invention pertains to Akkermansia muciniphila as the main commensal species distinguishing responders from progressors and its use alone or with E. hirae for the treatment of antibiotics or gut repertoire insufficiency-associated dysbiosis.

First claim

The invention claimed is:

1. A method of treating a cancer amenable to Nivolumab or Pembrolizumab anti-PD1 antibody therapy in a patient, comprising administering to the gut of the patient a fecal microbial composition comprising Akkermansia muciniphila bacteria, in combination with Nivolumab or Pembrolizumab anti-PD1 therapy.

2. The method of claim 1 , wherein the fecal microbial composition further comprises Enterococcus hirae bacteria.

3. The method of claim 1 , wherein the fecal microbial composition compensates dysbiosis in the cancer patient.

4. The method of claim 1 , wherein the fecal microbial composition induces immunostimulation in the cancer patient.

Assignees

• Roussy Inst Gustave
• Institut National De La Sante Et De La Rech Medicale—Inserm
• Univ Paris Saclay
• Institut National De Rech Pour Lagriculture Lalimentation Et Lenvironnement
• Inst Nat Sante Rech Med

Inventors

• Zitvogel Laurence
• Routy Bertrand
• Le Chatelier Emmanuelle

Classifications

• C12Q2600/118

  Prognosis of disease development · CPC title

• C12Q2600/106

  Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism · CPC title

• C12Q1/689

  for bacteria · CPC title

• C12Q1/6886 Primary

  for cancer (immunoassay for cancer G01N33/575) · CPC title

• A61K2039/585

  wherein the target is cancer · CPC title