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A bivalent single-chain Fv fragment against CD47 induces apoptosis for leukemic cells

2004; Elsevier BV; Volume: 315; Issue: 4 Linguagem: Inglês

10.1016/j.bbrc.2004.01.128

1090-2104

Yasufumi Kikuchi, Shinsuke Uno, Yasushi Yoshimura, Koji Otabe, Shinichiro Iida, Masayoshi Oh‐eda, Naoshi Fukushima, Masayuki Tsuchiya,

Erythrocyte Function and Pathophysiology

We constructed a single-chain antibody fragment (scFv) of murine monoclonal antibody, MABL, which specifically bound to human CD47 (hCD47) and induced apoptosis of the leukemic cells. The scFv of MABL antibody with a 15-residue linker (MABL scFv-15) formed both dimer (Mr 50 kDa) and monomer (Mr 25 kDa). Both MABL scFv-15 dimer and monomer had binding activity for hCD47. MABL scFv-15 dimer strongly induced apoptosis of hCD47-introduced mouse leukemic cells in vitro and exhibited anti-tumor effect in a myeloma transplanted mice model. However, MABL scFv-15 monomer scarcely exhibited these activities. These results strongly demonstrate that the ligation of CD47 antigen by two antigen-binding sites of MABL dimer is needed for inducing apoptosis. The parent MABL antibody caused hemagglutination due to the CD47 expressed on erythrocytes. Interestingly, MABL scFv-15 dimer did not cause hemagglutination. This apoptosis-inducing dimer appears to be a lead candidate for novel leukemic therapy.