Compositions and methods to enhance the immune system
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Publication Number
US-12060420-B2
Publication Date
2024-08-13
Expiration Date
Abstract
The invention relates to the field of molecular medicine. In particular, it relates to compositions and methods to enhance the clearance of aberrant cells, e.g. cancer cells or virus-infected cells, by the host's immune system. Provided is a composition comprising (i) a therapeutic compound that can trigger a host's immune effector cells against an aberrant cell, such as a therapeutic antibody, and (ii) at least one agent capable of reducing or preventing inhibitory signal transduction initiated via SIRPalpha.
Core Innovation
The invention relates to enhancing antibody-dependent cellular cytotoxicity (ADCC) by contacting a target diseased cell with an antibody that induces ADCC and with an antagonist of the CD47-SIRPα interaction. The antibody includes a human or non-human primate IgG Fc portion, and the contacting occurs in the presence of an effector cell. The antagonist comprises the N-terminal V-type immunoglobulin domain in SIRPα or in CD47.
The invention addresses inhibitory signaling from the CD47-SIRPα interaction that suppresses ADCC. By using a CD47-SIRPα antagonist containing the N-terminal V-type immunoglobulin domain, the approach reduces inhibitory signaling and thereby enhances ADCC and related immune clearance activities involving effector cells such as monocytes and macrophages.
The disclosed approach is applied to diseased cells including cancer cells and virus-infected cells. In the viral context, the discussion includes a hypothesized role of viral CD47 (vCD47) in poxvirus immune evasion and links this to potential enhancement of vaccine effectiveness.
Claims Coverage
The disclosed coverage centers on one independent claim directed to enhancing ADCC for diseased cells by co-contacting an ADCC-inducing human or non-human primate IgG Fc antibody and a CD47-SIRPα antagonist defined by the N-terminal V-type immunoglobulin domain. The dependent claims narrow the target to cancer, specify effector cell types, restrict IgG Fc subtype, and limit contacting conditions and context.
Enhancing ADCC with an IgG Fc antibody plus a CD47-SIRPα N-terminal V-type immunoglobulin domain antagonist
A method of enhancing antibody-dependent cellular cytotoxicity (ADCC) comprising contacting a target cell with an antibody comprising a human or non-human primate IgG Fc portion, wherein the antibody induces ADCC, and an antagonist of the CD47-SIRPα interaction, wherein said contacting occurs in the presence of an effector cell, wherein the target cell is a diseased cell, and wherein the antagonist comprises the N-terminal V-type immunoglobulin domain in SIRPα or the N-terminal V-type immunoglobulin domain in CD47.
Applying the ADCC-enhancing method to cancer cells
The method of enhancing ADCC wherein the target cell is a cancer cell as the diseased cell.
Using monocytes as the effector cell
The method of claim 1 wherein the effector cell is a monocyte.
Using macrophages as the effector cell
The method of claim 1 is specified such that the effector cell is a macrophage.
Restricting the antibody Fc portion to human IgG1 Fc
The method of claim 4 is further defined such that the human IgG Fc portion is specifically a human IgG1 Fc portion.
Contacting occurs in vitro
The method of claim 1 is performed such that the contacting step occurs in vitro.
Overall, the claim set focuses on enhancing ADCC by combining an ADCC-inducing IgG Fc antibody with a CD47-SIRPα antagonist that contains the N-terminal V-type immunoglobulin domain, with dependent claims narrowing the diseased context to cancer, selecting effector cell types (monocytes or macrophages), restricting the IgG Fc subtype (human IgG1), and limiting contacting to in vitro.
Stated Advantages
Enhances antibody-dependent cellular cytotoxicity (ADCC).
Reduces inhibitory signaling from the CD47-SIRPα interaction.
Improves immune clearance of aberrant cells, including cancer and virus-infected cells.
In viral settings, is linked to potential enhancement of vaccine effectiveness.
Documented Applications
Treatment/immune clearance settings for cancer cells as diseased cells using an ADCC-inducing antibody and a CD47-SIRPα antagonist containing the N-terminal V-type immunoglobulin domain.
Immune clearance settings for virus-infected cells, including discussion of viral CD47 (vCD47) in poxvirus immune evasion and potential enhancement of vaccine effectiveness.
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