Efficacy of anti-CD47 antibody-mediated phagocytosis with macrophages against primary effusion lymphoma

Hiroki Goto, Yuki Kojima, Kouki Matsuda, Ryusho Kariya, Manabu Taura, Kazuhiko Kuwahara, Hirokazu Nagai, Harutaka Katano, Seiji Okada

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20 Citations (Scopus)

Abstract

Background Recently, the critical role of CD47 on the surface of resistant cancer cells has been proposed in their evasion of immunosurveillance. Primary effusion lymphoma (PEL) is a subtype of aggressive non-Hodgkin lymphoma that shows serous lymphomatous effusion in body cavities, especially in advanced acquired immunodeficiency syndrome (AIDS). PEL is resistant to conventional chemotherapy and has a poor prognosis. In this study, we evaluated the effect of anti-CD47 antibody (Ab) on PEL in vitro and in vivo. Methods Surface CD47 of PEL cell lines was examined by flow cytometry. Efficacy of knocking down CD47 or anti-CD47 Ab-mediated phagocytosis against PEL was evaluated using mouse peritoneal macrophages and human macrophages in vitro. Primary PEL cells were injected intraperitoneally into NOD/Rag-2/Jak3 double-deficient (NRJ) mice to establish a direct xenograft mouse model. Results Surface CD47 of PEL cell lines was highly expressed. Knocking down CD47 and anti-CD47 Ab promoted phagocytic activities of macrophages in a CD47 expression-dependent manner in vitro. Treatment with anti-CD47 Ab inhibited ascite formation and organ invasion completely in vivo compared with control IgG-treated mice. Conclusion CD47 plays the pivotal role in the immune evasion of PEL cells in body cavities. Therapeutic antibody targeting of CD47 could be an effective therapy for PEL.

Original languageEnglish
Pages (from-to)1836-1846
Number of pages11
JournalEuropean Journal of Cancer
Volume50
Issue number10
DOIs
Publication statusPublished - 07-2014
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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    Goto, H., Kojima, Y., Matsuda, K., Kariya, R., Taura, M., Kuwahara, K., Nagai, H., Katano, H., & Okada, S. (2014). Efficacy of anti-CD47 antibody-mediated phagocytosis with macrophages against primary effusion lymphoma. European Journal of Cancer, 50(10), 1836-1846. https://doi.org/10.1016/j.ejca.2014.03.004