A bivalent single-chain Fv fragment against CD47 induces apoptosis for leukemic cells.
Biochem Biophys Res Commun
; 315(4): 912-8, 2004 Mar 19.
Article
in En
| MEDLINE
| ID: mdl-14985099
ABSTRACT
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.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Immunoglobulin Fragments
/
Leukemia L1210
/
Carrier Proteins
/
Antigens, CD
/
Apoptosis
Type of study:
Prognostic_studies
Language:
En
Journal:
Biochem Biophys Res Commun
Year:
2004
Document type:
Article
Affiliation country:
Japan