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bioRxiv · 10.1101/2019.12.18.881029

The characterization of a humanized rabbit anti-TNF α monoclonal antibody?A nationwide RA treatment drug study

wang, c.·Ni, x.·Liu, y.·Jin, z.·Xia, h.·N/A,
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Abstract

Tumor necrosis factor alpha (TNF) is now regarding as a key role in the pathogenesis of immune-mediated disease such as Rheumatoid arthritis (RA), Crohn's Disease, Psoriatic arthritis and Plaque Psoriasis. HERE we have successfully developed an anti-hTNF monoclonal rabbit antibody(HZ3M) with high binding and neutralizing activity based on RabMAbs platform. Rabbit hybridomas, immunized subcutanrously with 0.4 mg human TNF, were generated from the rabbit splenocytes and a total of 142 hybridoma clones with specific binding to human TNFa were obtained. The anti-TNFa RabMAbs showed better neutralizing activity and higher antigen binding affinity compared to Humira and Remicade, the elimination phase half-life 58.2h respectively. In vivo efficay studies, normal mice or human TNF-alpha transgenic mice were injected with 1.0 mg/kg Humira (positive control), HZ3M at 0.33?1.0 or 3.0 mg/kg, or solvent (negative control), showed that HZ3M is able to bind and neutralize hTNF in transgenic and normal mice as well as normal rabbits.Clearly dose-dependent response can be determined. Compared to marketed anti-TNFa drug Humira, the efficacy of HZ3M is seems to show significant longer holding time.Our observations indicate that the HZ3M derived from RabMAb preclinical safety study, and might have a therapeutic role in RA treatment.

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wang, c., Ni, x., Liu, y., Jin, z., Xia, h., N/A,. 2019-12-18. The characterization of a humanized rabbit anti-TNF α monoclonal antibody?A nationwide RA treatment drug study. https://doi.org/10.1101/2019.12.18.881029

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