Selection of high-affinity human monoclonal antibodies specific to the constant domain of versican as tools for tumor targeting

Antibody drugs with a high affinity and specificity are effective and safe for intractable diseases, such as cancers and autoimmune diseases. Furthermore, they have played a central role in drug discovery, currently accounting for eight of the top 20 pharmaceutical products worldwide by sales. Forty years ago, clinical trials on antibody drugs that were thought to be a magic bullet failed, partly due to the immunogenicity of monoclonal antibodies produced in mice. The recent breakthrough in antibody drugs is largely because of the contribution of phage display technology. Here, we reviewed the importance of phage display technology as a powerful platform for antibody drug discovery from various perspectives, such as the development of human monoclonal antibodies, affinity enhancement of monoclonal antibodies, and the identification of therapeutic targets for antibody drugs.

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Recombinant human monoclonal antibodies against different conformational epitopes of the E2 envelope glycoprotein of hepatitis C virus that inhibit its interaction with CD81

Journal of General Virology ◽

10.1099/0022-1317-81-10-2451 ◽

2000 ◽

Vol 81 (10) ◽

pp. 2451-2459 ◽

Cited By ~ 62

Author(s):

Tobias Allander ◽

Katarina Drakenberg ◽

Aster Beyene ◽

Domenico Rosa ◽

Sergio Abrignani ◽

...

Keyword(s):

Bone Marrow ◽

Monoclonal Antibodies ◽

Hepatitis C Virus ◽

Hepatitis C ◽

Envelope Glycoprotein ◽

Human Monoclonal Antibodies ◽

High Affinity ◽

Fab Fragments ◽

Genotype 1A

The antibody response to the envelope proteins of hepatitis C virus (HCV) may play an important role in controlling the infection. To allow molecular analyses of protective antibodies, we isolated human monoclonal antibodies to the E2 envelope glycoprotein of HCV from a combinatorial Fab library established from bone marrow of a chronically HCV-infected patient. Anti-E2 reactive clones were selected using recombinant E2 protein. The bone marrow donor carried HCV genotype 2b, and E2 used for selection was of genotype 1a. The antibody clones were expressed as Fab fragments in E. coli, and as Fab fragments and IgG1 in CHO cells. Seven different antibody clones were characterized, and shown to have high affinity for E2, genotype 1a. Three clones also had high affinity for E2 of genotype 1b. They all bind to conformation-dependent epitopes. Five clones compete for the same or overlapping binding sites, while two bind to one or two other epitopes of E2. Four clones corresponding to the different epitopes were tested as purified IgG1 for blocking the CD81–E2 interaction in vitro; all four were positive at 0·3–0·5 μg/ml. Thus, the present results suggest the existence of at least two conserved epitopes in E2 that mediate inhibition of the E2–CD81 interaction, of which one appeared immunodominant in this donor.

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Competitive Antigen Panning for Selection of HIV-1 Neutralizing Human Monoclonal Antibodies Specific for gp41

Therapeutic Antibodies - Methods in Molecular Biology™ ◽

10.1007/978-1-59745-554-1_9 ◽

2008 ◽

pp. 175-186

Author(s):

Mei-Yun Zhang ◽

Dimiter S. Dimitrov

Keyword(s):

Monoclonal Antibodies ◽

Human Monoclonal Antibodies ◽

Hiv 1 ◽

Selection Of

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