Anti-human SIRPα antibody is a new tool for cancer immunotherapy

Cancer Science
Yoji MurataTakashi Matozaki

Abstract

Interaction of signal regulatory protein α (SIRPα) expressed on the surface of macrophages with its ligand CD47 expressed on target cells negatively regulates phagocytosis of the latter cells by the former. We recently showed that blocking Abs to mouse SIRPα enhanced both the Ab-dependent cellular phagocytosis (ADCP) activity of mouse macrophages for Burkitt's lymphoma Raji cells opsonized with an Ab to CD20 (rituximab) in vitro as well as the inhibitory effect of rituximab on the growth of tumors formed by Raji cells in nonobese diabetic (NOD)/SCID mice. However, the effects of blocking Abs to human SIRPα in preclinical cancer models have remained unclear given that such Abs have failed to interact with endogenous SIRPα expressed on macrophages of immunodeficient mice. With the use of Rag2-/- γc-/- mice harboring a transgene for human SIRPα under the control of human regulatory elements (hSIRPα-DKO mice), we here show that a blocking Ab to human SIRPα significantly enhanced the ADCP activity of macrophages derived from these mice for human cancer cells. The anti-human SIRPα Ab also markedly enhanced the inhibitory effect of rituximab on the growth of tumors formed by Raji cells in hSIRPα-DKO mice. Our results thus suggest that...Continue Reading

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Citations

Jan 7, 2020·Nanoscale·Anujan RameshAshish Kulkarni
Aug 29, 2020·Advanced Materials·Yuqiong XiaXiaoyuan Chen
Sep 29, 2020·Expert Opinion on Biological Therapy·Victor I Seledtsov, Alexei von Delwig
Jan 11, 2020·Frontiers in Immunology·Elena Martin-OrozcoMaria Ayala-San Nicolas
Jun 7, 2019·International Journal of Molecular Sciences·Ryoji ItoSatoshi Nunomura
May 16, 2020·Journal of Immunology Research·Xiaojie LiBo Hu
Jan 13, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Gabriela AndrejevaDaniel S Pereira
Oct 20, 2020·The Journal of Clinical Investigation·Vanessa GauttierNicolas Poirier
Mar 26, 2021·Frontiers in Immunology·Chunye ZhangAaron C Ericsson

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Methods Mentioned

BETA
flow cytometry
PCR
ELISA
xenograft

Software Mentioned

GraphPad
GraphPad Prism
FlowJo

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