Effectiveness of anti-CD47 antibody and Ara-C combination targeting therapy NOD/SCID mouse of myeloid leukemia / 中国当代儿科杂志
Chinese Journal of Contemporary Pediatrics
; (12): 577-582, 2013.
Article
en Zh
| WPRIM
| ID: wpr-241469
Biblioteca responsable:
WPRO
ABSTRACT
<p><b>OBJECTIVE</b>To study the prognostic significance of CD47 in a NOD/SCID mouse model of acute myeloid leukemia (AML) and the best strategy for targeted therapy for this disease.</p><p><b>METHODS</b>CD34(+)CD38(-) leukemia stem cells (LSCs) were separated and transplanted into NOD/SCID mice to establish a mouse model of acute monocytic leukemia (AMoL). Anti-human CD47 antibody, alone or combined with cytosine arabinoside (Ara-C), was used to treat the mice with AMoL for 7-14 days, and therapeutic efficacy was assessed. LSCs were cultured together with mouse macrophages in culture medium containing anti-CD47 or anti-CD45 monoclonal antibody for 2 hours, to observe the phagocytic ability of macrophages to LSCs.</p><p><b>RESULTS</b>CD34(+)CD38(-) LSCs existed among THP-1 cells, with a content of about (0.12 ± 0.06)%, and a mouse model of AML was successfully established after the purified CD34(+)CD38(-) LSCs (97.0% ± 1.7%) were transplanted into NOD/SCID mice. The in vivo experiment showed that mice with AMoL had the most significant decrease in CD33(+)CD45(+) leukemia cells in peripheral blood and bone marrow and survived the longest after being treated with Ara-C (7 days) plus anti-CD47 monoclonal antibody (14 days) (P < 0.01). After 2 hours of in vitro culture, the phagocytic index in the culture medium containing anti-CD47 monoclonal antibody was significantly higher than in the culture medium containing anti-CD45 monoclonal antibody (76.9% ± 12.2% vs 7.60% ± 2.4%; P < 0.05).</p><p><b>CONCLUSIONS</b>High expression of CD47 is an adverse prognostic factor in AML. Combination therapy with anti-CD47 monoclonal antibody and Ara-C can effectively eliminate leukemia cells and LSCs, demonstrating great clinical significance in curing AML.</p>
Texto completo:
1
Base de datos:
WPRIM
Asunto principal:
Patología
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Fisiología
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Pronóstico
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Leucemia Mieloide Aguda
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Mortalidad
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Ratones SCID
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Ratones Endogámicos NOD
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Citarabina
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Quimioterapia
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Alergia e Inmunología
Tipo de estudio:
Prognostic_studies
Límite:
Animals
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Female
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Humans
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Male
Idioma:
Zh
Revista:
Chinese Journal of Contemporary Pediatrics
Año:
2013
Tipo del documento:
Article