Generation of a rabbit V(H) domain antibody polyspecific to c-Met and adenoviral knob protein.
Several types of bispecific antibodies with affinity to both adenoviral coat proteins and a targeted antigen have been developed with the aim of providing the specific delivery of adenoviral gene therapy vehicle. From a phage display library of combinatorial dAb2s (each with an anti-adenoviral knob protein V(H) fragment linked with an anti-c-Met V(H)), we serendipitously enriched and isolated a clone, JS5, that has polyspecificity such that it binds both the adenoviral knob protein and c-Met, despite having only one V(H) domain. Our indirect observations suggest that the polyspecificity of JS5 is developed through accumulation of antibody specificity. The method of sequential immunization of a rabbit, first with the adenoviral knob protein and then with target antigens, may provide a method by which monoclonal antibodies with stand-alone polyspecificity may be developed. Such targeted polyspecific antibodies could readily be used for re-directing adenoviral vectors to target cells.
Im
Shin-Young
SY
Cancer Research Institute, Seoul National University College of Medicine, 28 Yongon-Dong, Chongno-gu, Seoul, Republic of Korea.
Kim
Ki Su
KS
Yun
Chae-Ok
CO
Kim
Joo-Hang
JH
Yi
Kye-Sook
KS
Chung
Junho
J
D000256:Adenoviridae / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D018033:Antibodies, Bispecific; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000276:immunology*; D007135:Immunoglobulin Variable Region / Q000276:immunology*; D008969:Molecular Sequence Data; D019151:Peptide Library; D019859:Proto-Oncogene Proteins c-met / Q000276:immunology*; D011817:Rabbits; D014764:Viral Proteins / Q000276:immunology*
D018033:Antibodies, Bispecific; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D019151:Peptide Library; D014764:Viral Proteins; D019859:Proto-Oncogene Proteins c-met