A human antibody specific for SIRPα reprograms macrophages and promotes antibody mediated anti-cancer activity Journal Article

   

Authors:	Kurtz, K. G.; Lebedeva, I.; Pierre, S. A.; Andrew, D.; Liao, Y. R.; Ambriz, D.; Vergnolle, O.; Shen, L.; Nyakatura, E.; Baca, M.; Scheinberg, D. A.
Article Title:	A human antibody specific for SIRPα reprograms macrophages and promotes antibody mediated anti-cancer activity
Abstract:	Several T cell immune checkpoint blockade therapies have shown initial successes in multiple cancers. However, significant issues remain, including tumor relapse, severe toxicities, and a lack of efficacy in most patients. SIRPα, commonly known as the “do not eat me signal”, is a monocyte checkpoint cell surface protein. Agents that block the interaction of CD47 with SIRPα have recently shown clinical success in combination with monoclonal antibody therapy to potentiate macrophage phagocytosis of tumors. However, significant toxicities and logistical issues are associated with CD47-targeted agents due to the expression of CD47 on all human cells. In contrast, SIRPα has expression limited to myelomonocytic cells, meaning highly specific SIRPα blocking agents might reduce these toxicities and avoid the target antigen sink. Herein, we generated a high affinity and highly specific SIRPα-targeting monoclonal antibody, F05, that has enhanced SIRPα binding and reduced SIRPβ and SIRPγ binding capacity when compared to other available SIRPα antibodies. Furthermore, we show F05 reprograms immunosuppressive macrophages toward a phagocytic profile in vitro. F05 demonstrated efficacy in solid tumor animal models, providing a rationale for further development of the antibody. © 2025 Kurtz et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Journal Title:	PLoS ONE
Volume:	20
Issue:	5
ISSN:	1932-6203
Publisher:	Public Library of Science
Date Published:	2025-05-23
Start Page:	e0321169
Language:	English
DOI:	10.1371/journal.pone.0321169
PROVIDER:	scopus
PMCID:	PMC12101677
PUBMED:	40408355
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-105005747983&doi=10.1371%2fjournal.pone.0321169&partnerID=40&md5=06500081bd3484fe7a5d12a1b5f49e5a
Notes:	The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PubMed record and PDF. Corresponding MSK author is David A. Scheinberg -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/225549