Submitted October 23, 2008
Accepted November 30, 2008
In vivo efficacy of anti-MPL agonist antibody in promoting primary human hematopoietic cells
Masayuki Kai*, Tetsuya Hagiwara, Chie Emuta, Yukiko Chisaka, Kumi Tsuruhata, Chisato Endo, Yoshimasa Inagaki, Hiroshi Miyazaki, and Shiro Kataoka
Innovative Drug Research Laboratories, Kyowa Hakko Kirin Co.,Ltd., Takasaki, Japan
Frontier Laboratory, Kyowa Hakko Kirin Co.,Ltd., Takasaki, Japan
Business Development Department, Kyowa Hakko Kirin Co.,Ltd., Tokyo, Japan
* Corresponding author; email: masayuki.kai{at}kyowa-kirin.co.jp.
In a previous study, we generated novel anti-thrombopoietin receptor agonist antibodies as therapeutic candidates. In this report, we investigated the in vivo effects of one of these antibodies, MA01G4344U, on primary human hematopoietic cells using xenotransplantation. NOD/Shi-scid, IL-2R
null (NOG) mice were pretreated by total-body irradiation and transplanted with human cord blood-derived CD34+ cells. Weekly intraperitoneal injection of MA01G4344U (100 µg/mouse/week) or Peg-rhMGDF (5 µg/mouse/week) or phosphate buffered saline (PBS) was performed. Human cells in peripheral blood were analyzed by flow cytometry and bone marrow cells were analyzed by flow cytometry and colony assay. MA01G4344U successfully increased the number of human CD41+ platelets and human CD45+ cells in peripheral blood. In the bone marrow, MA01G4344U increased the number of human CD45+/CD34+ cells, which resulted in more multi-lineage progenitor cells. The efficacy of MA01G4344U in promoting primary human hematopoietic cells in vivo suggests its therapeutic potential for thrombocytopenic and pan-cytopenic disorders.
