TY - JOUR
T1 - Efficacy of anti-CD47 antibody-mediated phagocytosis with macrophages against primary effusion lymphoma
AU - Goto, Hiroki
AU - Kojima, Yuki
AU - Matsuda, Kouki
AU - Kariya, Ryusho
AU - Taura, Manabu
AU - Kuwahara, Kazuhiko
AU - Nagai, Hirokazu
AU - Katano, Harutaka
AU - Okada, Seiji
N1 - Funding Information:
We thank Ms. I. Suzu and Ms. S. Fujikawa for technical assistance and Ms. Y. Endo for secretarial assistance. This work was supported in part by a Health and Labour Sciences Research Grant from the Ministry of Health, Labour, and Welfare of Japan ( H25-AIDS-I-002 ), the Global COE program, ‘Global Education and Research Center Aiming at the Control of AIDS’, Grants-in-Aid for Science Research (No. 25114711 ) from the Ministry of Education, Science, Sports, and Culture of Japan , and the scholarship for the Graduate School of Medical Sciences, Kumamoto University, Japan.
PY - 2014/7
Y1 - 2014/7
N2 - 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.
AB - 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.
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U2 - 10.1016/j.ejca.2014.03.004
DO - 10.1016/j.ejca.2014.03.004
M3 - Article
C2 - 24726056
AN - SCOPUS:84901771670
VL - 50
SP - 1836
EP - 1846
JO - European Journal of Cancer
JF - European Journal of Cancer
SN - 0959-8049
IS - 10
ER -