Conventional Antibodies
Background
Mammals produce conventional antibodies made up of heavy and light chains which form the active tetramer. They can bind antigens with high affinity. Human antibodies can be sourced and cloned from B lymphocytes derived either from humans or transgenic mice expressing human heavy and light chain genes (Green et al., Nat. Genet., 1994; Mendez et al., Nat. Genet. 1997; Tomizuka et al., Proc. Natl. Acad. Sci., 2000 ) or obtained by a molecular biology strategy known as phage display.
Human antibodies derived from transgenic mice following antigen challenge using standard hybridoma technology are of high affinity and indistinguishable from those derived directly from man.
Harbour technology
Transgenic mice can be engineered so that functional endogenous murine antibody gene expression is reduced or eliminated, permitting the preferential expression of introduced transgenes encoding human H2L2 antibodies and (see below) human HCAb,s or camelised human HCAbs
Harbour Antibodies is developing propriety transgenic mouse strains capable of efficiently producing human HCAbs, camelised human HCAbs and human H2L2 antibodies following antigen challenge, in the absence of murine antibodies.
The introduction of human heavy and light chain transgene loci into an engineered mouse background results in the production, in response to antigen challenge, of either a single class of conventional human antibodies carrying a specific set of effector function (eg IgG or IgA), or multiple classes of antibodies (eg.IgM and IgG), dependent on the design of the introduced heavy chain immunoglobulin loci. Antigen specific H2L2 monoclonal antibodies can be recovered using standard hybridoma technology.
Strategy for the generation of transgenic mice producing transgene encoded H2L2 antibodies
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Harbour Antibodies