Combination tumor immunotherapy
AssigneeCheckmate Pharmaceuticals, Inc.
InventorArthur M. KRIEG
Life of this patent
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Abstract
Provided are methods for treating cancer using local administration of certain CpG oligonucleotides (CpG ODN) and systemic administration of a checkpoint inhibitor such as an anti-PD-1 antibody, an anti-PD-L1 antibody, and/or an anti-CTLA-4 antibody. In preferred embodiments, the CpG ODN are selected based on their propensity to induce high amounts of interferon alpha (IFN-α) and T-cell activation relative to interleukin-10 (IL-10) and B-cell activation. In certain embodiments, the methods further include pretreatment with radiotherapy, to potentiate the combination immunotherapy.
Claims69
A method of treating a cancerous tumor, comprising
- administering to a subject in need thereof an effective amount of a TLR9 agonist and a checkpoint inhibitor (CPI), wherein the TLR9 agonist is administered into or substantially adjacent to the tumor.
The method of any one of the preceding claims, wherein the TLR9 agonist is selected from the group consisting of A-class CpG DNA, C-class CpG DNA, E-class CpG DNA, A/E-class CpG DNA, P-class CpG DNA, and any combination thereof.
The method of any one of the preceding claims, wherein the CPI is administered systemically.
The method of any one of the preceding claims, wherein the CPI is an antibody or antigen-binding fragment thereof which binds specifically to an antigen selected from the group consisting of PD-1, PD-L1, and CTLA-4.
The method of any one of the preceding claims, wherein the TLR9 agonist is administered prior to administration of the CPI.
The method of any one of the preceding claims, wherein the cancerous tumor is a lymphoma or a cancerous tumor of a tissue or organ selected from the group consisting of skin, head and neck, esophagus, stomach, liver, colon, rectum, pancreas, lung, breast, cervix, ovary, kidney, bladder, prostate, thyroid, brain, muscle, and bone.
The method of any one of the preceding claims, wherein the cancerous tumor is melanoma.
The method of any one of the preceding claims, wherein the cancerous tumor is resistant to a treatment regimen comprising administration of the CPI without administration of the TLR9 agonist.
The method of any one of the preceding claims, wherein the subject is a human.
A method of treating a cancerous tumor, comprising
- administering to a subject in need thereof an effective amount of radiotherapy, a TLR9 agonist, and a checkpoint inhibitor (CPI), wherein the radiotherapy is initiated prior to administration of the TLR9 agonist, and the TLR9 agonist is administered into or substantially adjacent to the tumor.
A method of treating a cancerous tumor, comprising
- administering to a subject in need thereof an effective amount of a TLR9 agonist, a first checkpoint inhibitor (CPI), and a second CPI, wherein the TLR9 agonist and the first CPI are administered into or substantially adjacent to the tumor, and the second CPI is administered systemically.
Dependencies are inferred from the claim text.