Activatable cytokine constructs and combination methods

Activatable cytokine constructs combined with PD-1/PD-L1 inhibitors address the limitations of existing therapies by providing targeted cytokine activity in diseased tissues, reducing systemic toxicities and enhancing therapeutic efficacy against tumors.

AU2022360371B2Pending Publication Date: 2026-07-09CYTOMX THERAPEUTICS INC
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Patent Information

Application Number
AU2022360371
Authority / Receiving Office
AU · AU
Patent Type
Applications
Current Assignee / Owner
Priority Date
2022-04-07
Filing Date
2022-10-06
Publication Date
2026-07-09

AI Technical Summary

Technical Problem

Existing cytokine therapies, such as antibody-based treatments and interferon therapies, suffer from systemic toxicities and limited therapeutic effectiveness due to broad target expression and rapid clearance, while combination therapies with PD-1/PD-L1 inhibitors face challenges like non-responsive patients and tumor resistance, necessitating improved specificity and selectivity.

Method used

The use of activatable cytokine constructs (ACC) combined with PD-1/PD-L1 pathway inhibitors, comprising monomer constructs with peptide masks, mature cytokine proteins, and cleavable moieties, which are activated by proteases overexpressed in diseased tissues, allowing targeted cytokine activity in tumor microenvironments.

Benefits of technology

This approach reduces systemic toxicities, enables higher effective dosages, and increases therapeutic efficacy by enhancing cytokine activity specifically in diseased tissues, thereby reducing tumor growth and metastasis.

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Abstract

Provided herein are methods of treating a subject by administering a combination of an activatable cytokine construct (ACC) and a PD-1 / PD-L1 pathway inhibitor in which the ACC includes: a first monomer construct including an optional first peptide mask (PM1), an optional third cleavable moiety (CM3), a first mature cytokine protein (CP1), a first cleavable moiety (CM1), and a first dimerization domain (DD1), wherein the CM1 is positioned between the CP1 and the DD1; and a second monomer construct including an optional second peptide mask (PM2), an optional forth cleavable moiety (CM4), a second mature cytokine protein (CP2), a second cleavable moiety (CM2), and a second dimerization domain (DD2), wherein the CM2 is positioned between the CP2 and the DD2; wherein the DD1 and the DD2 bind to each other thereby forming a dimer of the first monomer construct and the second monomer construct; and where the ACC is characterized by a reduction in at least one activity of the CP1 and / or CP2 as compared to a control level of the at least one activity of the CP1 and / or CP2.
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