title: [Effectiveness of anti-CD47 antibody and Ara-C combination targeting therapy NOD/SCID mouse of myeloid leukemia].
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pediatrics, First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China. yingchaowang152@163.com.
authors.forename: Ying-Chao
authors.initials: YC
authors.lastname: Wang
authors.forename: Lei
authors.initials: L
authors.lastname: Feng
authors.forename: Chu-Yun
authors.initials: CY
authors.lastname: Yin
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Ma
authors.forename: Yong-Wei
authors.initials: YW
authors.lastname: Wei
authors.forename: Chun-Mei
authors.initials: CM
authors.lastname: Wang
authors.forename: Guang-Yao
authors.initials: GY
authors.lastname: Sheng
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D051928:CD47 Antigen / Q000276:immunology* / Q000502:physiology; D003561:Cytarabine / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D011379:Prognosis
chemical_list: D000911:Antibodies, Monoclonal; D051928:CD47 Antigen; D003561:Cytarabine