Compositions and methods to enhance the immune system

Inventors

van den Berg, Timo Kars

Assignees

Stichting Sanquin Bloedvoorziening

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 described invention provides a composition combining a therapeutic antibody comprising a human or non-human primate IgG Fc portion that induces antibody-dependent cellular cytotoxicity (ADCC) against a cancer cell, and at least one agent capable of reducing or preventing inhibitory signal transduction initiated via SIRPα. The SIRPα-inhibitory signaling agent is an anti-SIRPα antibody, or an anti-SIRPα binding Fab fragment, F(ab′)2 fragment, or scFv fragment.

The background problem addressed is that SIRPα-mediated inhibitory signaling suppresses immune effector functions that would otherwise clear cancer cells. By blocking CD47–SIRPα interaction, the invention aims to remove this inhibitory effect and thereby enhance immune clearance and tumor cell killing. The document states that blocking CD47–SIRPα signaling enhances phagocytosis/cytotoxicity and increases treatment efficacy.

The concept is supported with reported in vitro and in vivo findings, including ADCP/ADCC and in vivo tumor-killing data, and also extends to viral infection by targeting vCD47–SIRPα signaling. In this context, poxvirus/vaccinia virus related applications are described as benefiting from interruption of the vCD47–SIRPα inhibitory signaling pathway.

Claims Coverage

The partial content provides two independent claims. Each claim is centered on combining an ADCC-triggering therapeutic antibody with an agent that reduces or prevents SIRPα-initiated inhibitory signal transduction, with SIRPα antagonism via anti-SIRPα antibodies or defined antibody fragments.

Across the independent claims, the main inventive concept is the combination of an ADCC-capable therapeutic antibody with an anti-SIRPα agent that reduces or prevents SIRPα-mediated inhibitory signal transduction, where the anti-SIRPα component may be an antibody or an antibody fragment.

Stated Advantages

Documented Applications