Generation of High - Affinity Human Antibodies by Combining Donor - Derived and Synthetic Complementarity - Determining Region Diversity  

Oleh:

Hoet, Rene Michael ; Cohen, Edward H. ; Kent, Rachel Baribault ; Rookey, Kristin ; Schoonbroodt, Sonia ; Hogan, Shannon ; Rem, Louise ; Frans, Nicolas ; Daukandt, Marc ; Pieters, Henk ; Hegelsom, Rob van ; Neer, Nicole Coolen-van ; Nastri, Horacio G. ; Rondon, Isaac J. ; Leeds, Jennifer A. ; Hufton, Simon E. ; Huang, Lili ; Kashin, Irina ; Devlin, Mary ; Kuang, Guannan ; Steukers, Mieke ; Vismanathan, Malini ; Nixon, Andrew E. ; Sexton, Daniel J. ; Hoogenboom, Hennie R. ; Ladner, Robert Charles

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: Nature Biotechnology: The Science and Business of Biotechnology vol. 23 no. 3 (Mar. 2005), page 344-348.
Topik: antibodies; human antibodies; donor derived; synthetic complementary; region diversity

Ketersediaan

Perpustakaan Pusat (Semanggi) Nomor Panggil: NN9.2 Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

Lihat Detail Induk

Isi artikel

Combinatorial libraries of rearranged hypervariable Vh and Vl sequences from nonimmunized human donors contain antigen specificities, including anti self reactivities, created by random pairing of VHs and Vls. Somatic hypermutation of immunoglobin genes, however is critical in the generation of high affinity antibodies, are rarely found. Length in vitro affinity antibodies are rarely found. Lengthy invitro affinity maturation is often needed to improve antibodies from such libraries. We report the construction of human fab libraries having a unique combination of immunoglobulin sequences captured from human donors and synthetic diversity in key antigen contact sites in heavy chain complementarity determining regions 1 and 2. The success of this strategy is demonstrated by identifying many monovalent Fabs against multiple therapeutic targets show higher affinities than approved therapeutic antibodies. This very often circumvents the need for affinity maturation, accelerating discovery of antibody drug candidates.

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