![]() ![]() Antibody fragments with a Kd as low as 0.3 nM were subsequently isolated directly from this library. This library was constructed from antibody variable ( V) genes derived from 43 donors from B-cells derived from peripheral blood lymphocytes, tonsil and bone marrow. The first large (>10 10 distinct transformants) non-immunised phage display library capable of yielding high (sub-nanomolar) affinity antibody fragments to a given target was described in 1996 (CAT1.0 library) ( Vaughan et al., 1996). ![]() Large libraries of phage-displayed antibody fragments have proved to be a rich source of fully human antibodies for potential clinical development ( Edwards et al., 2003 Pukac et al., 2005 Thompson et al., 1999). Binding of these phage-displayed antibody fragments to an antigen of interest, followed by elution of the antibody–antigen complex allows the enrichment of antigen-specific antibodies. In order to generate human antibodies the two most commonly used technologies are immunisation of transgenic mice ( Gallo et al., 2000) and the generation and screening of large antibody fragment display libraries ( McCafferty et al., 1990 Marks et al., 1991). Human antibodies are an important class of therapeutics for a wide range of diseases, from cancers to autoimmune conditions such as rheumatoid arthritis ( Carter, 2006). However, following selection on the antigen panel, V H1– V λ1 germline family pairings are preferentially enriched and represent a remarkable 25% of the antigen-specific selected repertoire. ![]() The number of functional V H germlines and V κ light-chain germlines present is increased to 48/49 and 31/35, respectively, when selected V gene usage is included in the analysis. Germline diversity is broad with 45/49 functional V H germlines and 28/30 V λ and 30/35 V κ light-chain germlines represented in the sample. Analysis of a sample of >800 antibodies from the unselected library indicates V gene usage is representative of the human immune system with no strong bias towards any particular V H– V L pairing. This represents an average of ∼120 different functionally active antibodies per target. antagonism, agonism) of the target antigen. Over 5000 different target-specific antibodies were isolated to the 28 antigens with 3340 identified as modulating the biological function (e.g. A large 1.29 × 10 11 antibody fragment library, based upon variable ( V) genes isolated from human B-cells from 160 donors has been constructed and its performance measured against a panel of 28 different clinically relevant antigens. ![]()
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