Generation and characterization of a bispecific diabody targeting both EPH receptor A10 and CD3.
Biochem Biophys Res Commun
; 456(4): 908-12, 2015 Jan 24.
Article
in En
| MEDLINE
| ID: mdl-25528586
ABSTRACT
The EPH receptor A10 (EphA10) is up-regulated in breast cancer but is not normally expressed in healthy tissue, thus it has been suggested that EphA10 may be a useful target for cancer therapy. This study reports a diabody, an antibody derivative binding two different target molecules, EphA10 expressed in tumor cells and CD3 expressed in T cells, which showed T cell dependent-cytotoxicity. The diabody, which has His-tagged and FLAG-tagged chains, was expressed in Escherichia coli and purified in both heterodimer (Db-1) and homodimer (Db-2) formulations by liquid chromatography. Flow cytometry analysis using EphA10-expressing cells showed that binding activity of heterodimers was stronger than that of homodimers. Addition of diabodies to PBMC cultures resulted in T-cell mediated redirected lysis, and the bioactivity was consistent with the stronger binding activity of heterodimeric diabody formulations. Our results indicate that diabodies recognizing both EphA10 and CD3 could have a range of potential applications in cancer therapy, such as breast cancers that express the EPH receptor A10, especially triple negative breast cancer.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
CD3 Complex
/
Antibodies, Bispecific
/
Receptors, Eph Family
Limits:
Animals
/
Humans
Language:
En
Journal:
Biochem Biophys Res Commun
Year:
2015
Type:
Article
Affiliation country:
Japan