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.
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