Combination of a PD-1 antagonist and CpG-C type oligonucleotide for treating cancer
The present disclosure describes combination therapies comprising an antagonist of Programmed Death 1 receptor (PD-1) and a Toll-like receptor 9 (TLR9) agonist that is a CpG-C type oligonucleotide, and the use of the combination therapies for the treatment of cancer.
1. A method for treating cancer in an individual comprising administering to the individual a combination therapy which comprises a PD-1 antagonist and a TLR9 agonist, wherein:
the PD-1 antagonist is a monoclonal antibody, or antigen binding fragment thereof, which comprises: (a) light chain CDRs of SEQ ID NOs: 1, 2 and 3 and heavy chain CDRs of SEQ ID NOs: 4, 5 and 6; or (b) light chain CDRs of SEQ ID NOs: 7, 8 and 9 and heavy chain CDRs of SEQ ID NOs: 10, 11 and 12; and
the TLR9 agonist is a CpG-C type oligonucleotide, wherein the CpG-C type oligonucleotide comprises 5′-TCG N q TTCGA ACG TTC GAA CGT TCG AAT-3′ (SEQ ID NO: 66), wherein N are nucleosides and q=4.
2. The method of claim 1 , wherein the PD-1 antagonist is a monoclonal antibody, or an antigen binding fragment thereof, which specifically binds to human PD-1 and blocks the binding of human PD-L1 to human PD-1.
3. The method of claim 2 , wherein the PD-1 antagonist also blocks binding of human PD-L2 to human PD-1.
4. The method of claim 2 , wherein the PD-1 antagonist is an anti-PD-1 monoclonal antibody, which comprises a heavy chain and a light chain, and wherein the heavy chain comprises SEQ ID NO: 21 and the light chain comprises SEQ ID NO: 22.
5. The method of claim 2 , wherein the PD-1 antagonist is pembrolizumab or a pembrolizumab variant.
6. The method of claim 1 , wherein the CpG-C type oligonucleotide is a sodium salt, and the oligonucleotide is an oligodeoxynucleotide with a phosphorothioate backbone.
7. The method of claim 1 , wherein the cancer is a bladder cancer, a breast cancer, a clear cell kidney cancer, a head/neck a squamous cell carcinoma, a lung squamous cell carcinoma, a malignant melanoma, a non-small-cell lung cancer (NSCLC), an ovarian cancer, a pancreatic cancer, a prostate cancer, a renal cell cancer, a small-cell lung cancer (SCLC), or a triple negative breast cancer.
8. The method of claim 1 , wherein the cancer is an advanced or metastatic melanoma.
9. The method of claim 1 , wherein the cancer tests positive for human PD-L1.