Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
Background/Purpose: Antibodies may be functionalized using Affibody® molecules to create bispecific AffiMabs. We used protein engineering to develop single-construct biologics suitable for blocking inflammation driven by a combination of cytokines. AM201 is an AffiMab simultaneously targeting interleukin 6 (IL-6) and the tumor necrosis factor alpha (TNFα).
Methods: A set of affinity matured Affibody molecules binding to IL-6 were fused to either the N- or C-terminus of both the heavy and light chains of an anti-TNF monoclonal antibody based on adalimumab to produce bi-specific AffiMabs. Among these bi-specific antibodies, AM201 was determined on the basis of internal selection criteria including the efficacy and stability.
Results: AM201 blocks the interaction between complexes of the soluble IL-6 receptor (sIL-6Ra) and IL-6 and the co-receptor gp130 (IL-6 trans-signaling pathways) whilst it blocks IL-6 cis-signaling less potently. AM201 neutralize both TNFα and IL-6 simultaneously in vitro. AM201 was subsequently evaluated in an acute serum amyloid alpha (SAA) model in mice for in vivo activity. AM201 efficiently blocks combined IL-6 and TNF-triggered SAA secretion in vivo. We confirmed that AM201 potently reduce arthritic score in Tg197, human TNFα transgenic mouse. The quantitative PCR using human samples showed that AM201 efficiently block the gene expressions associated with bone removal including RANK, MMP9 and RANKL. We pursue efficacy test against non-human primate collagen-induced arthritis model and a drug development process with the aim to develop an innovative bi-specific AM201 simultaneously targeting TNFα and IL-6.
Conclusion: AM201 can be a novel potent therapeutic option for the treatment of rheumatoid arthritis patients who commonly develop aberrant expression of both TNFα and IL-6.
To cite this abstract in AMA style:Kim KT, Lee JS, Ko BK. Development of an Affimab Engineered to Simultaneously Target IL-6 and Tnfα for Therapeutic Use in Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 10). https://acrabstracts.org/abstract/development-of-an-affimab-engineered-to-simultaneously-target-il-6-and-tnf%ce%b1-for-therapeutic-use-in-rheumatoid-arthritis/. Accessed June 17, 2021.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/development-of-an-affimab-engineered-to-simultaneously-target-il-6-and-tnf%ce%b1-for-therapeutic-use-in-rheumatoid-arthritis/