Methods of treating tumors with a combination of il-7 protein and immune checkpoint inhibitors

Abstract

The present disclosure relates to methods of treating cancer (or tumor) with a combination of an IL-7 protein and an immune checkpoint inhibitor, such as a PD-1 antagonist (e.g., an anti-PD-1 antibody) or a CTLA-4 antagonist (e.g., an anti-CTLA-4 antibody).

Claims

1. Use of a combination of interleukin-7 (IL-7) protein and an anti-PD-1 antibody in the preparation of a medicament for the treatment of colorectal cancer, wherein the IL-7 protein comprises an oligopeptide of methionine-glycine-methionine (MGM), human IL-7, and a half-life extension moiety. in, The extended half-life portion is a mixed Fc, comprising a hinge region, a CH2 domain, and a CH3 domain. The hinge region includes a human IgD hinge region, the CH2 domain includes a portion of the human IgD CH2 domain and a portion of the human IgG4 CH2 domain, and the CH3 domain includes a portion of the human IgG4 CH3 domain. The IL-7 protein described herein consists of the amino acid sequence of SEQ ID NO:

24. The dosage of the IL-7 protein is said to be from 60 μg / kg to 1,440 μg / kg, and In this study, the tumor volume was reduced through the combined action of the IL-7 protein and the anti-PD-1 antibody.

2. The use according to claim 1, wherein the drug is also used to treat lymphopenia caused by or associated with a tumor, or lymphopenia caused by or associated with prior treatment of a tumor.

3. The use according to claim 1, wherein the anti-PD-1 antibody comprises nivolumab, pembrolizumab, MEDI0608, PDR001, BGB-A317 or any combination thereof.

4. The use according to claim 1, wherein the drug is prepared for administration of IL-7 protein simultaneously, sequentially, or prior to the anti-PD-1 antibody.

5. The use according to claim 1, The anti-PD-1 antibody is nivolumab, and the drug is prepared for administration at a fixed dose of about 240 mg every two weeks or about 480 mg every four weeks, or at a body weight-based dose of about 3 mg / kg every two weeks. The anti-PD-1 antibody is pembrolizumab, and the drug is prepared for administration at a fixed dose of about 200 mg every three weeks, or at a body weight-based dose of about 2 mg / kg every three weeks.

6. The use according to claim 1, wherein the drug is prepared for administration of IL-7 protein via parenteral, intramuscular, subcutaneous, ocular, intravenous, intraperitoneal, intradermal, intraorbital, intracranial, intraspinal, intraventricular, intrathecal, intracranial, intracisional, intracystic, intraspinal, intravenous, intrasheath, intracisional, intracystic, or intratumoral administration.

7. The use according to claim 1, wherein the drug is prepared for administration of anti-PD-1 antibodies via parenteral, intramuscular, subcutaneous, intravenous or intraperitoneal routes.

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