Methods of treatment with CD80 extracellular domain polypeptides
Inventors
Brennan, Thomas • Sennino, Barbara • Barbee, Susannah D. • Jeffry, Ursula
Assignees
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Publication Number
US-11789010-B2
Publication Date
2023-10-17
Expiration Date
Abstract
This application relates to use of CD80 (B7-1) extracellular domain (ECD) polypeptides and CD80-ECD fusion molecules and their use in methods of increasing the number of central memory T cells or for treatment for cancer or for use in cancer vaccine compositions.
Core Innovation
The invention relates to CD80 (B7-1) extracellular domain (ECD) and CD80-ECD fusion molecules for increasing central memory T cells (Tcm). The method administers a CD80 ECD fusion molecule to a subject, where the fusion molecule comprises a human CD80 ECD polypeptide and a human IgG1 Fc domain.
The approach includes assessing central memory T cell frequency and/or proliferation after administration. Central memory T cells are defined using markers such as CD95+ and CD28+, and proliferation is determined by measuring Ki67 expression at post-dose timepoints, including samples taken at least 7 days after dosing.
The disclosed embodiment includes nonhuman primate data showing dose-dependent expansion of CD4+ and CD8+ central memory T cells, with Ki67+ proliferation peaking around a post-dose timepoint. The CD80 ECD fusion molecules are further described with Fc domain characteristics and sialylation of 10 to 60 mol SA/mol protein, and the disclosed content links increasing central memory T cells to cancer treatment contexts, including solid tumors, combination with PD-1/PD-L1 inhibitors, and cancer vaccine compositions, including personalized cancer vaccine embodiments.
Claims Coverage
The partial content identifies one independent claim. It covers administering an effective amount of a CD80 ECD fusion molecule to increase central memory T cell frequency and/or proliferation, with multiple dependent claim refinements that specify measurement of proliferation, timing, sequence and sialylation properties, and combination treatment contexts.
Administering an effective amount of a CD80 ECD fusion molecule for increasing central memory T cell frequency and/or proliferation
Administering a CD80 extracellular domain (ECD) fusion molecule to the subject in an amount effective to increase Tcm frequency and/or proliferation, wherein the CD80 ECD fusion molecule comprises a human CD80 ECD polypeptide and a human IgG1 Fc domain.
Detecting increased central memory T cell proliferation at a post-administration timepoint
Detecting increased central memory T cell proliferation in a subject sample taken at least 7 days after administration of the CD80 ECD fusion molecule.
Determining central memory T cell proliferation by Ki67 expression
Determining central memory T cell proliferation by measuring Ki67 expression.
Using a CD80 ECD polypeptide with SEQ ID NO:5
Providing a human CD80 ECD polypeptide having the amino acid sequence of SEQ ID NO:5.
Employing a CD80 ECD fusion molecule having 10 to 60 sialic acid molecules
Specifying that the CD80 ECD fusion molecule includes 10 to 60 sialic acid (SA) molecules.
Combining with a PD-1/PD-L1 inhibitor
Administering the CD80 ECD fusion molecule together with a PD-1/PD-L1 inhibitor.
Overall, the claim coverage centers on using a human CD80 ECD fused to a human IgG1 Fc domain to increase central memory T cells (frequency and/or proliferation), with dependent limitations that define how proliferation is determined (Ki67), a post-dose timing threshold (at least 7 days), specific CD80 ECD sequence (SEQ ID NO:5), a sialylation range (10 to 60 SA molecules), and combination with PD-1/PD-L1 inhibitors.
Stated Advantages
Increases central memory T cell (Tcm) frequency and/or proliferation in a subject.
Allows assessment of central memory T cell proliferation using Ki67 expression at defined post-administration timepoints.
Supports dose-dependent expansion of CD4+ and CD8+ central memory T cells with measurable Ki67+ proliferation after dosing.
Documented Applications
Cancer treatment, including solid tumors, using the described approach to increase central memory T cells.
Combination cancer therapy with PD-1/PD-L1 inhibitors.
Cancer vaccine compositions, including personalized cancer vaccine embodiments.
Nonhuman primate use in cynomolgus monkeys (Macaca fascicularis), with observations of CD4+ and CD8+ central memory T cell expansion after dosing.
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