Checkpoint Blockade and Microsatellite Instability

• US 20170267760A1
• Filed: 06/01/2017
• Published: 09/21/2017
• Est. Priority Date: 11/13/2014
• Status: Abandoned Application

• Current Assignee: Johns Hopkins University
• Original Assignee: Johns Hopkins University
• Inventors: Diaz, Luis, Vogelstein, Bert, Kinzler, Kenneth W., Papadopoulos, Nickolas, Le, Dung
• Application Number:
  US15/611,017
• Publication Number:
  US 20170267760A1
• Time in Patent Office: Days
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2039/55 characterised by the host/recipient, e.g. newborn with maternal antibodies
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 13/08 of the prostate
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07K 16/2803 against the immunoglobulin superfamily
• CPC Class Codes: C07K 16/2818 against CD28 or CD152
• CPC Class Codes: C07K 16/2827 against B7 molecules, e.g. CD80, CD86
• CPC Class Codes: C07K 16/30 from tumour cells
• CPC Class Codes: C07K 16/40 against enzymes
• CPC Class Codes: C07K 2317/00 Immunoglobulins specific features
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C12Q 1/6886 for cancer immunoassay for cancer G01N33/574
• CPC Class Codes: C12Q 2600/106 Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
• CPC Class Codes: C12Q 2600/156 Polymorphic or mutational markers
• CPC Class Codes: C12Y 113/11052 Indoleamine 2,3-dioxygenase (1.13.11.52), i.e. indoleamine 2,3-dioxygenase 1

Abstract

Blockade of immune checkpoints such as cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed death-1 (PD-1) shows promise in patients with cancer. Inhibitory antibodies directed at these receptors have been shown to break immune tolerance and promote anti-tumor immunity. These agents work particularly well in patients with a certain category of tumor. Such tumors may be particularly susceptible to treatment because of the multitude of neoantigens which they produce.

Claims

1. A method for treating cancer, the method comprising:

testing one or more microsatellite markers in a tumor sample from a patient;

determining microsatellite instability (MSI) for the tumor based on the testing; and

identifying the patient as a candidate for treatment with an immune checkpoint inhibitor when the tumor exhibits an MSI phenotype.

2. The method of claim 1, further comprising administering the immune checkpoint inhibitor to the patient.

3. The method of claim 1, wherein the immune checkpoint inhibitor comprises an antibody.

4. The method of claim 3, wherein the antibody is selected from the group consisting of:

an anti-PD-1 antibody;

an anti-IDO antibody;

anti-CTLA-4 antibody;

an anti-PD-L1 antibody; and

an anti-LAG-3 antibody.

5. The method of claim 1, wherein the one or more microsatellite markers are selected from the group consisting of BAT-25, BAT-26, MONO-27, NR-21, NR-24, Penta C, and Penta D.

6. The method of claim 1, wherein the tumor is determined to display the MSI phenotype when the testing indicates at least 100 mutations in a genome of the tumor relative to normal tissue of the patient.

7. The method of claim 1, wherein the cancer is selected from the group consisting of:

colon, gastric, endometrial, cholangiocarcinoma, pancreatic, and prostate cancer.

8. The method of claim 1, wherein the immune checkpoint inhibitor comprises an antibody selected from the group consisting of:

a humanized monoclonal antibody;

sMK-3475; and

an IgG4 antibody.

9. The method of claim 1, wherein a plurality of microsatellite markers is tested.

10. The method of claim 9, wherein the plurality of microsatellite markers is each selected from the group consisting of BAT-25, BAT-26, MONO-27, NR-21, NR-24, Penta C, and Penta D.

11. The method of claim 9, wherein the plurality of microsatellite markers comprises BAT-25, BAT-26, MONO-27, NR-21, NR-24, Penta C, and Penta D.

12. The method of claim 1, wherein testing the one or more microsatellite markers includes one technique selected from the group consisting of an immunohistochemistry (IHC) assay, a PCR test, and next generation sequencing.