- Antibodies derived from non-animal sources or transgenic animals carry a limited repertoire of human IgG gene family only and maintain artificial antibody sequences that neither exist in nature nor will be selected by murine antigen presenting cells in a murine environment.
Non-nature-selected antibody sequences may work well in vitro but frequently they will behave completely different in vivo. One of the common problems of artificial antibodies used as medicines is a disadvantageous (clinical) pharmacokinetic profile. Often, such antibodies even disappear in vivo without trackable disposition. Furthermore antibodies carrying residual non-human sequences are more likely to induce anti-drug antibodies in humans, which may cause immunogenicity related adverse events.
Reconstitution of immune-deficient mice* with human hematopoietic stem cells - e.g. CD133+ cells - develop a fully functional human immune system (humanized mouse).
Following immunization the humanized mouse directly generates high quality, high-affinity, and fully human antibodies. These antibodies are pre-selected by human immune cells in vivo. Therefore in vitro affinity maturation and antibody humanization processes - a costly and tedious effort required following alternative approaches - can be avoided for antibodies envisaged as medicinal products in humans.
Being not inbred, Humanized Mice have no blind spots in their immune repertoires, meaning that diverse antibodies covering virtually any target epitope can be found – even on highly complex targets.
The variable (V) regions of conventional antibodies from Humanized Mice are naturally encoded by the complete repertoire of V genes found in humans – unlike transgenic mice.
An in-depth characterization of the reconstituted immune system by data analysis of deep sequencing Ig repertoire validated the humanized mouse be immunological equivalent to human donors
While proteins of therapeutic interest are often conserved between human and rodent and tolerated, they are not tolerated in Humanized Mice, based on the post-natal time point for the human immune system development where all differentiation/embryonic, oncofetal or developmental proteins are not expressed anymore. This makes Humanized Mice able to mount antibody responses against any therapeutic target
- Directhumab holds IP-rights for this novel technology, which opens the direct access to fully human antibodies.
- Our proprietary technology has expansive potential to immediately generate fully human antibodies against a wide range of antigens, including developmental and embryonic antigens.
- For research groups and biotechnology companies interested in the development of novel antibodies for medicinal use this is a unique opportunity to benefit from an independent IP-position.
- We invite partners interested in exploring this promising technology.
Inquiries to discuss modalities for collaboration are welcome.
* (e.g. Rag2-/-gamma chain-/- with inactivated mouse antibody machinery)
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