Pharmaceutical composition for cancer treatment comprising fusion protein including IL-2 protein and CD80 protein and anticancer drug
Inventors
Jang, Myung Ho • Nam, Su Youn • Koh, Young Jun
Assignees
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Publication Number
US-11857601-B2
Publication Date
2024-01-02
Expiration Date
Abstract
A pharmaceutical composition containing, as active ingredients, a fusion protein including an IL-2 protein and a CD80 protein, and an anticancer agent is disclosed. A fusion protein including a CD80 fragment, an immunoglobulin Fc, and an IL-2 variant, can activate immune cells such as natural killer cells, and at the same time, can control the immune cell regulatory activity of regulatory T cells. In addition, when an anticancer agent is administered in combination with the fusion protein, cancer can be effectively inhibited. Therefore, a pharmaceutical composition containing, as active ingredients, a fusion protein of an IL-2 protein and a CD80 protein, and an anticancer agent can increase the immune activity in the body and can be effectively utilized not only for cancer but also for an infectious disease, and thus has high industrial potential.
Core Innovation
The invention provides a pharmaceutical composition comprising, as active ingredients, a fusion protein dimer comprising a CD80 fragment and an IL-2 variant, and an anticancer agent. The CD80 fragment is an extracellular domain of CD80 protein, and the IL-2 variant comprises the amino acid sequence of SEQ ID NO: 10 with substitutions R38A and F42A.
The fusion protein dimer is defined by structural formula (I) or (II), including an Fc domain, peptide linkers (1) and (2), and integers n and m each independently 0 or 1. In the structural formula, X corresponds to the extracellular domain of CD80 and Y corresponds to the IL-2 variant.
The composition is used in combination with diverse anticancer agents, including an anti-PD-1 antibody, an anti-PD-L1 antibody, an anti-TIGIT antibody, VEGFR inhibitors, EGFR inhibitors, PARP inhibitors, DNA methyltransferase inhibitors, TGFβ receptor inhibitors, CDK4/6 inhibitors, STING agonists, alkylating agents, microtubule inhibitors, antimetabolites, topoisomerase inhibitors, and combinations thereof.
Claims Coverage
One independent claim is identified. It covers a pharmaceutical composition with two core inventive features: a specifically defined CD80/IL-2 fusion protein dimer and an anticancer agent selected from a listed group or combinations thereof.
Cd80 extracellular domain fused to an il-2 variant with r38a and f42a
A fusion protein dimer comprising a CD80 fragment that is an extracellular domain of CD80 protein and an IL-2 variant comprising the amino acid sequence of SEQ ID NO: 10 with substitutions of R38A and F42A.
Specified structural formula with fc domain and peptide linkers
The fusion protein has structural formula (I) or (II) in which the Fc domain is included, linkers (1) and (2) are peptide linkers, and n and m are each independently 0 or 1, with X as the extracellular domain of CD80 and Y as the IL-2 variant.
Fusion protein dimer combined with selected anticancer agents
A pharmaceutical composition comprising the fusion protein dimer together with an anticancer agent selected from the group consisting of an anti-PD-1 antibody, an anti-PD-L1 antibody, an anti-TIGIT antibody, a VEGFR inhibitor, an EGFR inhibitor, a PARP inhibitor, a DNA methyltransferase inhibitor, a TGF-β receptor inhibitor, a CDK4/6 inhibitor, a STING agonist, an alkylating agent, a microtubule inhibitor, an antimetabolite, a topoisomerase inhibitor, and combinations thereof.
The claim coverage centers on a CD80 extracellular domain fragment fused to an IL-2 variant defined as SEQ ID NO: 10 with R38A and F42A, a specified structural arrangement including an Fc domain and peptide linkers with n and m each 0 or 1, and combination with an anticancer agent broadly selected from named immuno-oncology and anticancer drug classes and their combinations.
Stated Advantages
The combination therapy shows significantly greater tumor growth inhibition and improved tumor growth inhibition rates compared with monotherapy or vehicle in specified days/groups.
Statistical significance and survival outcomes are reported for certain models, including combinations involving mGI-101 paired with DMXAA.
Documented Applications
In vitro cytotoxicity assays are described for combination use of the fusion protein dimer (GI-101/mGI-101) with selected anticancer agents.
In vivo tumor growth inhibition is described for combination therapy using GI-101/mGI-101 with selected anticancer agents across multiple tumor models, including CT26, LL/2, and Renca.
Survival outcomes are described for certain models for specific combinations, including mGI-101 combined with DMXAA.
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