Improvement in affinity and thermostability of a fully human antibody against interleukin-17A by yeast-display technology and CDR grafting
Monoclonal antibodies (mAbs) are widely used in many fields due to their high specificity and ability to recognize a broad range of antigens. IL-17A can induce a rapid inflammatory response both alone and synergistically with other proinflammatory cytokines. Accumulating evidence suggests that thera...
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Elsevier,
2019-09-01T00:00:00Z.
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| LEADER | 00000 am a22000003u 4500 | ||
|---|---|---|---|
| 001 | doaj_2660168b3b4849f6bb641c2038f5cd8c | ||
| 042 | |a dc | ||
| 100 | 1 | 0 | |a Wei Sun |e author |
| 700 | 1 | 0 | |a Zhaona Yang |e author |
| 700 | 1 | 0 | |a Heng Lin |e author |
| 700 | 1 | 0 | |a Ming Liu |e author |
| 700 | 1 | 0 | |a Chenxi Zhao |e author |
| 700 | 1 | 0 | |a Xueying Hou |e author |
| 700 | 1 | 0 | |a Zhuowei Hu |e author |
| 700 | 1 | 0 | |a Bing Cui |e author |
| 245 | 0 | 0 | |a Improvement in affinity and thermostability of a fully human antibody against interleukin-17A by yeast-display technology and CDR grafting |
| 260 | |b Elsevier, |c 2019-09-01T00:00:00Z. | ||
| 500 | |a 2211-3835 | ||
| 500 | |a 10.1016/j.apsb.2019.02.007 | ||
| 520 | |a Monoclonal antibodies (mAbs) are widely used in many fields due to their high specificity and ability to recognize a broad range of antigens. IL-17A can induce a rapid inflammatory response both alone and synergistically with other proinflammatory cytokines. Accumulating evidence suggests that therapeutic intervention of IL-17A signaling offers an attractive treatment option for autoimmune diseases and cancer. Here, we present a combinatorial approach for optimizing the affinity and thermostability of a novel anti-hIL-17A antibody. From a large naïve phage-displayed library, we isolated the anti-IL-17A mAb 7H9 that can neutralize the effects of recombinant human IL-17A. However, the modest neutralization potency and poor thermostability limit its therapeutic applications. In vitro affinity optimization was then used to generate 8D3 by using yeast-displayed random mutagenesis libraries. This resulted in four key amino acid changes and provided an approximately 15-fold potency increase in a cell-based neutralization assay. Complementarity-determining regions (CDRs) of 8D3 were further grafted onto the stable framework of the huFv 4D5 to improve thermostability. The resulting hybrid antibody 9NT/S has superior stabilization and affinities beyond its original antibody. Human fibrosarcoma cell-based assays and in vivo analyses in mice indicated that the anti-IL-17A antibody 9NT/S efficiently inhibited the secretion of IL-17A-induced proinflammatory cytokines. Therefore, this lead anti-IL-17A mAb might be used as a potential best-in-class candidate for treating IL-17A related diseases. KEY WORDS: Monoclonal antibody, Antibody maturation, Phage display, Yeast surface display, CDR grafting, Antibody engineering | ||
| 546 | |a EN | ||
| 690 | |a Therapeutics. Pharmacology | ||
| 690 | |a RM1-950 | ||
| 655 | 7 | |a article |2 local | |
| 786 | 0 | |n Acta Pharmaceutica Sinica B, Vol 9, Iss 5, Pp 960-972 (2019) | |
| 787 | 0 | |n http://www.sciencedirect.com/science/article/pii/S2211383518311729 | |
| 787 | 0 | |n https://doaj.org/toc/2211-3835 | |
| 856 | 4 | 1 | |u https://doaj.org/article/2660168b3b4849f6bb641c2038f5cd8c |z Connect to this object online. |