Anti-SIRPα antibodies as a potential new tool for cancer immunotherapy

Tadahiko Yanagita, Yoji Murata, Daisuke Tanaka, Sei ichiro Motegi, Eri Arai, Edwin Widyanto Daniwijaya, Daisuke Hazama, Ken Washio, Yasuyuki Saito, Takenori Kotani, Hiroshi Ohnishi, Per Arne Oldenborg, Noel Verjan Garcia, Masayuki Miyasaka, Osamu Ishikawa, Yae Kanai, Takahide Komori, Takashi Matozaki

Research output: Contribution to journalArticle

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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+ 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.

Original languageEnglish
Article numbere89140
JournalJCI Insight
Volume2
Issue number1
DOIs
Publication statusPublished - 2017 Jan 1

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Immunotherapy
Anti-Idiotypic Antibodies
Neoplasms
Macrophages
Phagocytosis
Renal Cell Carcinoma
Melanoma
Cytophagocytosis
Natural Killer Cells
Cell Death
Ligands
T-Lymphocytes
Therapeutics
Proteins

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Yanagita, T., Murata, Y., Tanaka, D., Motegi, S. I., Arai, E., Daniwijaya, E. W., ... Matozaki, T. (2017). Anti-SIRPα antibodies as a potential new tool for cancer immunotherapy. JCI Insight, 2(1), [e89140]. https://doi.org/10.1172/jci.insight.89140

Anti-SIRPα antibodies as a potential new tool for cancer immunotherapy. / Yanagita, Tadahiko; Murata, Yoji; Tanaka, Daisuke; Motegi, Sei ichiro; Arai, Eri; Daniwijaya, Edwin Widyanto; Hazama, Daisuke; Washio, Ken; Saito, Yasuyuki; Kotani, Takenori; Ohnishi, Hiroshi; Oldenborg, Per Arne; Garcia, Noel Verjan; Miyasaka, Masayuki; Ishikawa, Osamu; Kanai, Yae; Komori, Takahide; Matozaki, Takashi.

In: JCI Insight, Vol. 2, No. 1, e89140, 01.01.2017.

Research output: Contribution to journalArticle

Yanagita, T, Murata, Y, Tanaka, D, Motegi, SI, Arai, E, Daniwijaya, EW, Hazama, D, Washio, K, Saito, Y, Kotani, T, Ohnishi, H, Oldenborg, PA, Garcia, NV, Miyasaka, M, Ishikawa, O, Kanai, Y, Komori, T & Matozaki, T 2017, 'Anti-SIRPα antibodies as a potential new tool for cancer immunotherapy', JCI Insight, vol. 2, no. 1, e89140. https://doi.org/10.1172/jci.insight.89140
Yanagita T, Murata Y, Tanaka D, Motegi SI, Arai E, Daniwijaya EW et al. Anti-SIRPα antibodies as a potential new tool for cancer immunotherapy. JCI Insight. 2017 Jan 1;2(1). e89140. https://doi.org/10.1172/jci.insight.89140
Yanagita, Tadahiko ; Murata, Yoji ; Tanaka, Daisuke ; Motegi, Sei ichiro ; Arai, Eri ; Daniwijaya, Edwin Widyanto ; Hazama, Daisuke ; Washio, Ken ; Saito, Yasuyuki ; Kotani, Takenori ; Ohnishi, Hiroshi ; Oldenborg, Per Arne ; Garcia, Noel Verjan ; Miyasaka, Masayuki ; Ishikawa, Osamu ; Kanai, Yae ; Komori, Takahide ; Matozaki, Takashi. / Anti-SIRPα antibodies as a potential new tool for cancer immunotherapy. In: JCI Insight. 2017 ; Vol. 2, No. 1.
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