PMID: 9636296Nov 1, 1995Paper

Rapid assay of phage-derived recombinant human fabs as bispecific antibodies

Bio/technology
P P SannaD R Burton

Abstract

Specific anti-tumor and anti-viral activities can be conferred on lymphocytic and myeloid effector cells by retargeting them with bispecific antibodies. These are antibodies which possess an anti-target binding region and a region capable of binding specific effector cell surface markers. For the rapid evaluation of recombinant human Fabs as bispecific antibodies, we have constructed a vector that allows for the conversion of Fabs into protein A fusion proteins. These can be used to generate bispecific antibodies when complexed to appropriate anti-effector cell immunoglobulins. As a model system, a protein A fusion derivative of a human recombinant anti-herpes simplex virus (HSV) Fab was constructed and complexed to OKT3, a T cell-activating antibody specific for CD3. This complex reduced HSV-2 yields in infected cells by about three logs relative to controls when incubated on HSV-2-infected cell monolayers in the presence of IL-2-activated lymphocytes. The system described allows for the rapid evaluation of recombinant human Fabs as bispecific antibodies for therapeutic applications. In addition, Fab-protein A fusion proteins can be used in ELISA and other immuno-assays with increased sensitivity.

References

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Citations

Aug 27, 1998·Molecular Biotechnology·Y LiG C Whitelam
Sep 13, 1996·Journal of Immunological Methods·S M KipriyanovG Moldenhauer
Sep 1, 1996·Nature Biotechnology·B T McGuinnessH R Hoogenboom

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