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.
Xie
Xuemei
X
School of Environmental Sciences, University of Guelph, 50 Stone Road East, Guelph, Ontario N1G 2W1, Canada.
Weisser
Nina E
NE
McLean
Michael D
MD
Hall
J Christopher
JC
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