Functional characterization of the selective pan-allele anti-SIRPα antibody ADU-1805 that blocks the SIRPα-CD47 innate immune checkpoint.

ABSTRACT:

Background

Accumulating preclinical data indicate that targeting the SIRPα/CD47 axis alone or in combination with existing targeted therapies or immune checkpoint inhibitors enhances tumor rejection. Although several CD47-targeting agents are currently in phase I clinical trials and demonstrate activity in combination therapy, high and frequent dosing was required and safety signals (acute anemia, thrombocytopenia) were recorded frequently as adverse events. Based on the restricted expression pattern of SIRPα we hypothesized that antibodies targeting SIRPα might avoid some of the concerns noted for CD47-targeting agents.

Methods

SIRPα-targeting antibodies were generated and characterized for binding to human SIRPα alleles and blockade of the interaction with CD47. Functional

SUBMITTER: Voets E 

PROVIDER: S-EPMC6894304 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature