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Anti-SIRP α antibodies as a potential new tool for cancer immunotherapy.
- Source :
-
JCI insight [JCI Insight] 2017 Jan 12; Vol. 2 (1), pp. e89140. Date of Electronic Publication: 2017 Jan 12. - Publication Year :
- 2017
-
Abstract
- Tumor cells are thought to evade immune surveillance through interaction with immune cells. Much recent attention has focused on the modification of immune responses as a basis for new cancer treatments. SIRPα is an Ig superfamily protein that inhibits phagocytosis in macrophages upon interaction with its ligand CD47 expressed on the surface of target cells. Here, we show that SIRPα is highly expressed in human renal cell carcinoma and melanoma. Furthermore, an anti-SIRPα Ab that blocks the interaction with CD47 markedly suppressed tumor formation by renal cell carcinoma or melanoma cells in immunocompetent syngeneic mice. This inhibitory effect of the Ab appeared to be mediated by dual mechanisms: direct induction of Ab-dependent cellular phagocytosis of tumor cells by macrophages and blockade of CD47-SIRPα signaling that negatively regulates such phagocytosis. The antitumor effect of the Ab was greatly attenuated by selective depletion not only of macrophages but also of NK cells or CD8 <superscript>+</superscript> T cells. In addition, the anti-SIRPα Ab also enhances the inhibitory effects of Abs against CD20 and programmed cell death 1 (PD-1) on tumor formation in mice injected with SIRPα-nonexpressing tumor cells. Anti-SIRPα Abs thus warrant further study as a potential new therapy for a broad range of cancers.<br />Competing Interests: The authors have declared that no conflict of interest exists.
- Subjects :
- Adult
Aged
Aged, 80 and over
Animals
Antigens, Differentiation immunology
Antigens, Differentiation metabolism
Antigens, Differentiation therapeutic use
CD47 Antigen drug effects
CD8-Positive T-Lymphocytes drug effects
Carcinoma, Renal Cell metabolism
Female
Humans
Macrophages drug effects
Macrophages metabolism
Male
Melanoma metabolism
Mice
Middle Aged
Neoplasms immunology
Phagocytosis drug effects
Receptors, Immunologic immunology
Receptors, Immunologic metabolism
Receptors, Immunologic therapeutic use
Tumor Microenvironment immunology
CD47 Antigen metabolism
CD8-Positive T-Lymphocytes metabolism
Immunotherapy methods
Neoplasms therapy
Receptors, Immunologic antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 2379-3708
- Volume :
- 2
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- JCI insight
- Publication Type :
- Academic Journal
- Accession number :
- 28097229
- Full Text :
- https://doi.org/10.1172/jci.insight.89140