CD47 targeted therapies for the treatment of infectious disease
Inventors
Weiskopf, Kipp Andrew • Hasenkrug, Kim J. • Stoddart, Cheryl A. • McCune, Joseph M. • Weissman, Irving L.
Assignees
University of California San Diego UCSD • Leland Stanford Junior University • US Department of Health and Human Services
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Publication Number
US-12410259-B2
Publication Date
2025-09-09
Expiration Date
Abstract
Methods are provided for treating a subject with for an intracellular pathogen infection, by administering an agent that reduces the binding of CD47 on a infected cell to SIRPα on a host phagocytic cell, in an effective dose for increasing the phagocytosis of infected cells.
Core Innovation
The invention relates to treating a mammalian subject for intracellular pathogen infection by administering an anti-CD47 agent that reduces the binding of CD47 on an infected cell to SIRPα on a phagocytic cell. By reducing this CD47-SIRPα interaction on intracellularly infected cells, the method increases phagocytosis of the infected cell and promotes clearance. The approach targets the “don’t eat me” signal associated with CD47 signaling.
The anti-CD47 agent is provided as an anti-CD47 antibody; an anti-SIRPα antibody that does not stimulate signaling through SIRPα; a modified SIRPα polypeptide that specifically binds to CD47; or a soluble CD47 polypeptide that specifically binds to SIRPα and does not stimulate signaling through SIRPα. The document further frames the role of increased CD47 on target cells as part of the mechanism for modulating phagocytosis.
Supportive disclosure includes that infections upregulate CD47 on infected versus uninfected cells, as assessed by FACS/recombinant SIRPα-Fc binding across multiple infections including Friend virus, Fr98, HIV, La Crosse virus, and Chlamydia. The document also describes an in vivo antiviral evaluation using a humanized anti-CD47 monoclonal antibody (5F9-hIgG4) in an SCID-hu Thy/Liv HIV mouse model, shown in FIG. 7.
Claims Coverage
The partial claims provided include one independent claim directed to treating mammalian subjects with intracellular pathogen infection using an anti-CD47 agent to reduce CD47-SIRPα binding and increase phagocytosis. The claim identifies multiple alternative anti-CD47 agent types and specifies an effective dose range.
Reducing CD47 binding to SIRPα to increase phagocytosis
Administering to the subject an anti-CD47 agent that reduces the binding of CD47 on an infected cell to SIRPα on a phagocytic cell at an effective dose for increasing the phagocytosis of the infected cell.
Anti-CD47 agent modalities
The anti-CD47 agent is an anti-CD47 antibody; or an anti-SIRPα antibody that does not stimulate signaling through SIRPα; or a modified SIRPα polypeptide that specifically binds to CD47; or a soluble CD47 polypeptide that specifically binds to SIRPα and does not stimulate signaling through SIRPα.
Treating mammalian subjects with intracellular pathogen infection (bacterium)
Treating a mammalian subject for intracellular pathogen infection wherein the pathogen is a bacterium.
The claim coverage focuses on therapeutic treatment of intracellular bacterium infection by administering an anti-CD47 agent that reduces CD47 binding to SIRPα on phagocytic cells to increase phagocytosis, with the anti-CD47 agent defined by alternative antibody or soluble/modified polypeptide modalities that either specifically bind CD47 or avoid stimulating SIRPα signaling.
Stated Advantages
Increasing the phagocytosis of the infected cell.
Documented Applications
Treating a mammalian subject for intracellular pathogen infection, where the pathogen is a bacterium.
Reducing infection-associated “don’t eat me” signaling by blocking CD47-SIRPα signaling to promote clearance of intracellularly infected cells.
In vivo antiviral evaluation using a humanized anti-CD47 monoclonal antibody (5F9-hIgG4) in an SCID-hu Thy/Liv HIV mouse model.
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