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Background The pathogenic bacteria Staph. aureus and Strep. pyogenes each express proteolytic enzymes with actions against IgGs of the host. The proteases, gluV8 and IdeS, respectively, inactivate host antibodies by just a single hinge cleavage. Although ADCC and complement functions of IgGs are greatly reduced, this potent bacterial evasion tactic is successfully reversed by a host immune mechanism. In a model of S. aureus infection, we found that rabbits readily mount immune responses against the cleavage site induced by gluV8. Actual suppression of in vivo colony growth was afforded by such anti-hinge antibodies. The explanation was that anti-hinge antibodies form a complex with cleaved, targeting Abs on the S. aureus surface to restore effector killing functions. The key connection is anti-hinge (‘damage site’) antibodies. A parallel strategy for human tumor therapy is envisioned using human anti-hinge Abs (HAH).Methods HAH Abs are readily demonstrable by ELISA in individual and pooled IgGs (IVIg). HAH Abs bind to the IdeS-cleaved hinge to restore and even amplify cell killing functions (ADCC, CDC) aided by a highly efficacious IgG3 component. Thus, endogenous immunity is poised to act when it encounters IdeS-mediated damage to host IgGs on cell surfaces, particularly cancer cells.Results Evidence for enhanced cell killing includes 1) restored B-cell clearance by IdeS-cleaved rituximab in non-human primates, 2) enhanced killing when IdeS-pretreated mAbs such as trastuzumab were exposed to cancer cell lines in the presence of IVIg plus human NK cells; 3) restored function to IdeS-inactivated anti-cancer mAbs already bound to target cells before exposure to IVIg and NKs, and 4) recruitment of anti-tumor Abs themselves from IVIg followed by subsequent exposure of the cells to IdeS, IVIg and NKs. In the latter case, the identities and specificities of the anti-tumor Abs in IVIg were undetermined but capable of inducing cell death via the IdeS/HAH assemblage.Conclusions The adaptive immune system inherently possesses two critical resources --anti-cancer IgGs and HAH-- to piece together a potent anti-tumor mechanism. To complete it, only Ides-cleaved IgG on the tumor surface is missing. The convergence of human and bacterial components described here may underlie our ability to fight off recurrent S. pyogenes exposures. It also calls to mind the paradoxical observations of the regression of solid tumors concurrent with S. pyogenes infections (Coley’s toxin). We submit that this ordering of discrete immune components is a novel and unexplored approach to tumor therapy.Acknowledgements We acknowledge the contributions of Elizabeth Olesin of BioMere for in vitro assays.Ethics Approval Studies in monkeys were non-terminal and were approved by the ethics review committee of Biomere.