HuCAL® Immunoglobulins

Ig Conversions

We can convert HuCAL Fab antibody candidates into full-length human or chimeric antibodies when an Fc region is required for your application. The variable heavy and light chain genes are cloned into vectors with the desired constant regions and co-transfected for expression in mammalian cells. Purified human immunoglobulins in your chosen isotype can be delivered in as little as 10 weeks after generation of the HuCAL Fab antibodies.

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Fully human HuCAL immunoglobulins of various isotypes are produced entirely in vitro, with secure and unlimited supply. This makes them ideal for pharmaceutical drug development and human immunoassay applications, examples of which are detailed below.

Controls and Calibrators

HuCAL antibodies can be used to replace patient sera as a consistent, secure, and fully-characterized source of control human antibodies for immunoassays. They have been successfully used as control and calibrator reagents in quantitative autoimmune and infectious disease assays. A direct comparison between patient sera and recombinant human IgA against cardiolipin antibodies has recently been published, Ann N Y Acad Sci. 1173:190-8.

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Watch our webinar to find out how fully human recombinant antibodies can be custom-made as positive controls and calibrators for immunodiagnostic assays

Chimeric Surrogate Antibodies

Therapeutic drug development may require in vivo validation of target antibody interactions in animal models. Our technology makes it possible to combine HuCAL Fab candidates with a murine or rat Fc region, thus converting them into full length chimeric human-mouse and human-rat antibodies. The chimeric antibodies help to facilitate therapeutic target validation in these animal species.

PK Tools

With HuCAL technology it is possible to develop a single high-affinity antibody for use first as a Fab reagent for pharmacokinetic (PK) studies, and later convert it to a fully human positive immunoglobulin control for immunogenicity testing. This eliminates the need for patient or animal sera and greatly reduces assay development time and effort.

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Fully Human Standards for Immunogenicity Testing

HuCAL Fab antibody candidates can easily be converted into a range of full length human immunoglobulin isotypes (IgA, IgE, IgG or IgM) to create the ideal standards for the evaluation of anti-drug antibody (ADA) responses in immunogencitiy testing. Since IgA and IgM isotypes are available, it is possible to monitor the potential immune response in greater detail.

Anti-ID Antibody Mimicking an ADA Response

In the image below, an anti-idiotypic (ID) antibody was used as a positive control standard and spiked into pooled non-human primate plasma. The anti-ID antibody is mimicking an anti-drug antibody (ADA) response in a homogeneous bridging immunogenicity assay.

An anti human CD38 target drug antibody was used in a biotinylated format as a capture reagent and in an ECL labeled format as a detection antibody. Both antibodies were incubated together with the spiked plasma samples and the complexes captured on Streptavidin.

The anti-ID antibody bridges the two labeled anti human CD38 drug candidates thus creating a reference curve. The signal shows a rapid linear increase which declines at highest anti-ID antibody concentrations due to the well described quenching “hook effect” in the one step incubation format.

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A schematic diagram of the HuCAL ADA generation process, when used to create anti-idiotypic antibodies, is available here.