Transchromosomal™ (TC) Technology - Background
KHK's TC™ Technology is a broad platform that is based on KHK's proprietary microcell mediated chromosome transfer (MMCT) technology that is capable of introducing large portions of the human chromosome into any animal, such as a mouse or a cow. Using the MMCT technology as a basis, KHK has applied it to the development of a transchromosomic mouse (the KM Mouse™) that is capable of generating fully human monoclonal antibodies, and to the development of a transchromosomic cow that will be capable of generating fully human polyclonal antibodies.
The KM Mouse™
A powerful drug discovery tool, the KM Mouse™ was developed through KHK's strategic alliance with Medarex, Inc. The result of cross-breeding KHK's TC Mouse™ with Medarex's HuMAb Mouse, the KM Mouse™ carries the human chromosome 14 fragment from the TC Mouse™ representing the complete locus for the human immunoglobulin heavy chain and the Igκ transgene from the HuMAb Mouse (The KM Mouse™ has its own antibody producing genes inactivated). The KM Mouse™ has improved stability of the human immunoglobulin chains and can produce high affinity, fully human antibodies representing the majority of the Ig subclasses (IgG1, IgG2, IgG3, IgG4, IgA, etc.). The KM Mouse™ can generate fully human antibodies to a wide variety of human antigens within a few months of immunization, and the resulting antibodies are fully functional and have high affinity, requiring no further optimization.
Expanding upon the KM Mouse™ platform, KHK has developed variations to the KM Mouse™ in order to meet specific antibody generation needs:
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HAC (Human Artificial Chromosome) Mouse
Utilizing KHK's proprietary human artificial chromosome (HAC) technology, the λHAC KM Mouse™ has been developed which carries the λHAC as well as the Ig-κ transgene, creating a antibody-producing mouse that contains all three components of the human immunoglobulin loci.
Here at KKC, our scientists are applying the KM Mouse™ technology towards the development of novel and therapeutically useful monoclonal antibodies to treat cancer, autoimmune diseases and infectious diseases.
Hematech, Inc. - The TC Cow
Human polyclonal antibody products, such as intravenous immunoglobulin (IVIG) and hyperimmune immunoglobulin (HI), are currently in use as therapeutics for the treatment of various immune deficiencies and viral diseases. However, IVIG and HI are currently only available from human donors, and the shortage in their supply, along with their variablity, has limited their use. KHK is applying its MMCT technology to the development of a TC bovine (TC Cow) that will have the ability to generate fully human antibodies. In developing the TC Cow, the cow's own immunoglobulin genes have been inactivated and replaced with a human artificial chromosome representing the entire unrearranged sequence of the human immunoglobulin loci for both the antibody heavy and light chain. The TC Cow will be able to produce unlimited quantities of consistent fully human polyclonal antibodies cost effectively that can be used to treat a wide variety of diseases.
KKC's sister subsidiary, Hematech, Inc. based in Sioux Falls, South Dakota, is developing this exciting new technology platform. For more information, please visit: www.hematech.com.
