Compositions and methods for tumor immunotherapy

Inventors

Krieg, Arthur • Morris, Aaron • Mauro, David • Weiner, George • Milhem, Mohammed

Assignees

Checkmate Pharmaceuticals Inc

Abstract

Provided are compositions and methods for treating cancer using administration of certain volumes of CpG oligonucleotides (CpG ODN) and, optionally, 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-a) 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.

Core Innovation

The patent describes tumor immunotherapy in which a toll-like receptor 9 (TLR9) agonist is administered as CpG oligonucleotides (CpG ODN) for intratumoral or peritumoral treatment of a tumor environment. The CpG ODN are engineered to drive high type I interferon, including IFN-α, and to promote T-cell activation while reducing IL-10 and B-cell activation relative to B-class CpG ODN. The approach is framed around converting a “cold” tumor microenvironment into a “hot” tumor microenvironment.

The patent further describes that high-IFN CpG ODN delivered intratumorally increases tumor-infiltrating lymphocytes and CD8+ T-cell infiltration, which is stated to be predictive of checkpoint inhibitor (CPI) response. It also describes mitigation of IL-10–mediated immune suppression to improve synergy with checkpoint blockade and/or radiotherapy. The described mechanistic rationale is tied to Th1-like tumor microenvironment formation and immune activation.

In addition, the patent describes formulation of CpG ODN as virus-like particles (VLP), including VLP for CpG ODN such as CMP-001, and compositions associated with broader checkpoint inhibitor antibody combinations. It further describes CpG ODN structural and backbone design considerations, including CpG class selection (A-class, E-class, and A/E-class) and backbone linkage types (phosphodiester vs phosphorothioate), to modulate IRF versus NF-κB signaling, IFN-α versus IL-10 induction, nuclease stability, and local inflammation control.

Claims Coverage

The partial content includes one independent claim (clm-00001). The independent claim requires five core inventive elements: treating lymphoma in a subject, administering a TLR9 agonist with an A-class CpG DNA sequence comprising SEQ ID NO: 82, formulating the TLR9 agonist as a virus-like particle (VLP), delivering it by intratumoral or peritumoral injection, and administering a specified administration volume of 5 mL together with a stated dosing range per administration.

Across the single independent claim in the provided partial content, the claimed inventive concept centers on treating lymphoma using a VLP-formulated TLR9 agonist containing an A-class CpG DNA sequence (SEQ ID NO: 82), delivered by intratumoral or peritumoral injection at about 1 mg to about 100 mg per administration in a volume of 5 mL.

Stated Advantages

Documented Applications

No documented applications found