Compositions and methods to enhance the immune system
Inventors
Assignees
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Publication Number
US-10287351-B2
Publication Date
2019-05-14
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 disclosed invention enhances in vivo efficacy of a therapeutic antibody to induce cancer cell destruction by antibody-dependent cellular cytotoxicity (ADCC) in a human subject receiving anti-cancer treatment with a therapeutic antibody comprising a human or non-human primate IgG Fc portion. The therapeutic antibody induces ADCC, and an agent capable of reducing or preventing inhibitory signal transduction initiated via SIRPα is administered in an amount sufficient to increase ADCC.
The invention addresses cancer therapy by pairing ADCC-inducing therapeutic antibodies with an agent that reduces or prevents SIRPα inhibitory signaling via the CD47–SIRPα axis. The agent is an anti-CD47 antibody or an antigen-binding fragment thereof, including a Fab fragment or a F(ab')2 fragment, and it is administered prior to, simultaneously, or after the therapeutic antibody.
In addition to method embodiments, the disclosed subject matter includes a composition comprising a therapeutic antibody capable of inducing cancer cell destruction by ADCC and an agent capable of reducing or preventing inhibitory signal transduction initiated via SIRPα. In the composition, the agent is an anti-CD47 antibody or an antigen-binding fragment thereof, including Fab or F(ab')2 fragments.
Claims Coverage
The provided set includes three independent claims. Each independent claim centers on an ADCC-inducing therapeutic antibody together with an agent that reduces or prevents inhibitory signal transduction initiated via SIRPα, with the SIRPα-modulating agent specified as an anti-CD47 antibody or antigen-binding fragments.
Enhancing in vivo ADCC efficacy via SIRPα inhibitory-pathway modulation
A method of enhancing in vivo efficacy of a therapeutic antibody to induce cancer cell destruction by antibody-dependent cellular cytotoxicity (ADCC) in a human subject receiving anti-cancer treatment with a therapeutic antibody comprising a human or non-human primate IgG Fc portion, wherein the therapeutic antibody induces ADCC; administering prior to, simultaneously, or after the therapeutic antibody an agent capable of reducing or preventing inhibitory signal transduction initiated via SIRPα, in an amount sufficient to increase ADCC, wherein the agent is an anti-CD47 antibody, a Fab fragment thereof, or a F(ab')2 fragment thereof.
Treating cancer with selected therapeutic antibodies plus anti-CD47 targeting
A method of treating cancer in a subject receiving anti-cancer treatment with a therapeutic antibody selected from the group consisting of rituximab, trastuzumab, alemtuzumab, bevacizumab, cetuximab, and panitumumab; administering to the human subject prior to, simultaneously, or after the administration of the therapeutic antibody, an anti-CD47 antibody, a Fab fragment thereof, or a F(ab')2 fragment thereof.
ADCC-inducing therapeutic antibody composition with SIRPα inhibitory-pathway agent
A composition comprising a therapeutic antibody comprising a human or non-human primate IgG Fc portion, wherein the therapeutic antibody is capable of inducing cancer cell destruction by antibody-dependent cellular cytotoxicity (ADCC), and an agent capable of reducing or preventing inhibitory signal transduction initiated via SIRPα, wherein the agent is an anti-CD47 antibody, a Fab fragment thereof, or a F(ab')2 fragment thereof.
Across the independent claims, the core inventive coverage combines an ADCC-capable therapeutic antibody with an anti-CD47 (or Fab or F(ab')2) agent that reduces or prevents inhibitory signal transduction initiated via SIRPα, administered before, simultaneously, or after the therapeutic antibody, and optionally embodied as a composition containing both components.
Stated Advantages
Increases ADCC such that the in vivo efficacy of the therapeutic antibody to induce cancer cell destruction by ADCC is enhanced.
Documented Applications
Treating cancer in a human subject receiving anti-cancer treatment with an ADCC-inducing therapeutic antibody by administering an anti-CD47 antibody (or Fab or F(ab')2 fragment) that reduces or prevents inhibitory signal transduction initiated via SIRPα.
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