Complexes with anti-epitope tag IgGs improve the therapeutic potential of epitope-tagged antibody fragments.
The use of recombinant antibody fragments (rAbF) as therapeutic agents is compromised by shorter serum persistences than IgG therapeutics and their inability to mediate Fc-dependent effector functions. Here, we show that the strategy of complex formation between epitope-tagged rAbFs and anti-epitope IgG monoclonal antibodies (mAb) can improve the therapeutic potential of rAbFs by both enhancing their serum persistence and conferring on them the ability to recruit Fc-mediated effector functions. These two mechanistic aspects of this strategy were demonstrated using c-myc- and 6xHis-tagged Fab and scFv rAbFs, both directed against Pseudomonas aeruginosa O6ad, in combination with two different murine anti-epitope tag IgGs, anti-5xHis IgG (Penta-His) and anti-c-myc IgG (9E10). Further enhancement of this strategy for the employment of rAbFs as therapeutics is discussed.
School of Environmental Sciences, University of Guelph, 50 Stone Road East, Guelph, Ontario N1G 2W1, Canada.
Xuemei
X
Xie
Nina E
NE
Weisser
Michael D
MD
McLean
J Christopher
JC
Hall
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D002460:Cell Line; D000939:Epitopes / Q000276:immunology*; D007128:Immunoglobulin Fragments / Q000276:immunology / Q000627:therapeutic use*; D051379:Mice; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000276:immunology; D011550:Pseudomonas aeruginosa / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology / Q000627:therapeutic use
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D000939:Epitopes; D007128:Immunoglobulin Fragments; D011994:Recombinant Proteins; C048844:anti-IgG