A trivalent anti-erbB2/anti-CD16 bispecific antibody retargeting NK cells against human breast cancer cells.
Bispecific antibody (BsAb) can physically cross-link immune cells to tumor cells, circumventing the proper structures for tumor cell-immune cell interactions and activating the cellular cytotoxic mechanisms. The optimal BsAb should target tumor cells with high affinity, but activate trigger molecules on cytotoxic cells by monovalent binding of Fab fragments. In the present study, a trivalent anti-erbB2/anti-CD16 BsAb was produced. This BsAb possesses bivalent arms specifically binding to the extracellular domain of erbB2 and monovalent Fab fragment redirecting NK cells. The recombinant protein could be expressed and purified from Escherichia coli as native proteins without refolding. It was fully functional in bispecific binding to SKBR3 and NK cells. The molecular size of this trivalent BsAb protein is larger than diabody and smaller than whole antibody and expected to have advantages for both high penetration of small antibody fragments and the slow circulation clearance of whole antibody. This novel protein may be an attractive target for further improvement and evaluation.
Xie
Zhigang
Z
Department of Molecular Immunology, Institute of Basic Medical Sciences, Taiping Road 27, Beijing 100850, PR China.
Shi
Ming
M
Feng
Jiannan
J
Yu
Ming
M
Sun
Yingxun
Y
Shen
Beifen
B
Guo
Ning
N
D018033:Antibodies, Bispecific / Q000276:immunology* / Q000302:isolation & purification* / Q000378:metabolism; D001943:Breast Neoplasms / Q000276:immunology* / Q000378:metabolism; D045744:Cell Line, Tumor; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D015202:Protein Engineering / Q000379:methods*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology* / Q000378:metabolism; D017452:Receptors, IgG / Q000276:immunology* / Q000378:metabolism
D018033:Antibodies, Bispecific; D018719:Erb-b2 Receptor Tyrosine Kinases; D017452:Receptors, IgG