3wd5 Citations

Comparison of the inhibition mechanisms of adalimumab and infliximab in treating tumor necrosis factor α-associated diseases from a molecular view.

J. Biol. Chem. 288 27059-67 (2013)
Cited: 22 times
EuropePMC logo PMID: 23943614


TNFα-targeting therapy with the use of the drugs Etanercept, Infliximab, and Adalimumab is used in the clinical treatment of various inflammatory and immune diseases. Although all of these reagents function to disrupt the interaction between TNFα and its receptors, clinical investigations showed the advantages of Adalimumab treatment compared with Etanercept and Infliximab. However, the underlying molecular mechanism of action of Adalimumab remains unclear. In our previous work, we presented structural data on how Infliximab binds with the E-F loop of TNFα and functions as a TNFα receptor-binding blocker. To further elucidate the variations between TNFα inhibitors, we solved the crystal structure of TNFα in complex with Adalimumab Fab. The structural observation and the mutagenesis analysis provided direct evidence for identifying the Adalimumab epitope on TNFα and revealed the mechanism of Adalimumab inhibition of TNFα by occupying the TNFα receptor-binding site. The larger antigen-antibody interface in TNFα Adalimumab also provided information at a molecular level for further understanding the clinical advantages of Adalimumab therapy compared with Infliximab.

Reviews citing this publication (1)

  1. Current approaches to fine mapping of antigen-antibody interactions. Abbott WM, Damschroder MM, Lowe DC. Immunology 142 526-535 (2014)

Articles citing this publication (21)

  1. The antibody response against human and chimeric anti-TNF therapeutic antibodies primarily targets the TNF binding region. van Schie KA, Hart MH, de Groot ER, Kruithof S, Aarden LA, Wolbink GJ, Rispens T. Ann. Rheum. Dis. 74 311-314 (2015)
  2. Structural and molecular basis for Ebola virus neutralization by protective human antibodies. Misasi J, Gilman MS, Kanekiyo M, Gui M, Cagigi A, Mulangu S, Corti D, Ledgerwood JE, Lanzavecchia A, Cunningham J, Muyembe-Tamfun JJ, Baxa U, Graham BS, Xiang Y, Sullivan NJ, McLellan JS. Science 351 1343-1346 (2016)
  3. A general strategy for generating intact, full-length IgG antibodies that penetrate into the cytosol of living cells. Choi DK, Bae J, Shin SM, Shin JY, Kim S, Kim YS. MAbs 6 1402-1414 (2014)
  4. Insights into HER2 signaling from step-by-step optimization of anti-HER2 antibodies. Fu W, Wang Y, Zhang Y, Xiong L, Takeda H, Ding L, Xu Q, He L, Tan W, Bethune AN, Zhou L. MAbs 6 978-990 (2014)
  5. A generic approach to engineer antibody pH-switches using combinatorial histidine scanning libraries and yeast display. Schröter C, Günther R, Rhiel L, Becker S, Toleikis L, Doerner A, Becker J, Schönemann A, Nasu D, Neuteboom B, Kolmar H, Hock B. MAbs 7 138-151 (2015)
  6. Real-life experience with switching TNF-α inhibitors in ankylosing spondylitis. Gulyas K, Bodnar N, Nagy Z, Szamosi S, Horvath A, Vancsa A, Vegh E, Szabo Z, Szucs G, Szekanecz Z, Szanto S. Eur J Health Econ 15 Suppl 1 S93-100 (2014)
  7. Systematic screening of soluble expression of antibody fragments in the cytoplasm of E. coli. Gaciarz A, Veijola J, Uchida Y, Saaranen MJ, Wang C, Hörkkö S, Ruddock LW. Microb. Cell Fact. 15 22 (2016)
  8. LMO1 is a novel oncogene in colorectal cancer and its overexpression is a new predictive marker for anti-EGFR therapy. Liu J, Yan P, Jing N, Yang J. Tumour Biol. 35 8161-8167 (2014)
  9. Structural basis of checkpoint blockade by monoclonal antibodies in cancer immunotherapy. Lee JY, Lee HT, Shin W, Chae J, Choi J, Kim SH, Lim H, Won Heo T, Park KY, Lee YJ, Ryu SE, Son JY, Lee JU, Heo YS. Nat Commun 7 13354 (2016)
  10. Simple NMR methods for evaluating higher order structures of monoclonal antibody therapeutics with quinary structure. Chen K, Long DS, Lute SC, Levy MJ, Brorson KA, Keire DA. J Pharm Biomed Anal 128 398-407 (2016)
  11. Anti-TNF drives regulatory T cell expansion by paradoxically promoting membrane TNF-TNF-RII binding in rheumatoid arthritis. Nguyen DX, Ehrenstein MR. J. Exp. Med. 213 1241-1253 (2016)
  12. Cell-free production and streamlined assay of cytosol-penetrating antibodies. Min SE, Lee KH, Park SW, Yoo TH, Oh CH, Park JH, Yang SY, Kim YS, Kim DM. Biotechnol. Bioeng. 113 2107-2112 (2016)
  13. Efficacy of Adalimumab in a Girl with Refractory Intestinal Behcet's Disease. Kaji M, Kishi T, Miyamae T, Nagata S, Yamanaka H, Fujikawa S. Case Rep Rheumatol 2015 716138 (2015)
  14. Predicting Hemagglutinin MHC-II Ligand Analogues in Anti-TNFα Biologics: Implications for Immunogenicity of Pharmaceutical Proteins. Andrick BJ, Schwab AI, Cauley B, O'Donnell LA, Meng WS. PLoS ONE 10 e0135451 (2015)
  15. Rational design of antirheumatic prodrugs specific for sites of inflammation. Onuoha SC, Ferrari M, Sblattero D, Pitzalis C. 67 2661-2672 (2015)
  16. Oncogenicity of LHX2 in pancreatic ductal adenocarcinoma. Zhou F, Gou S, Xiong J, Wu H, Wang C, Liu T. Mol. Biol. Rep. 41 8163-8167 (2014)
  17. LMO1 is a novel oncogene in lung cancer, and its overexpression is a new predictive marker for anti-EGFR therapy. Zhang Y, Yang J, Wang J, Guo H, Jing N. Med. Oncol. 31 99 (2014)
  18. Expression, purification, crystallization and preliminary X-ray analysis of the HER3-9E12 Fab complex. He K, Huang A, Huang Y, Takeda H. Acta Crystallogr F Struct Biol Commun 70 786-789 (2014)
  19. Combinatorial immunotherapy of sorafenib and blockade of programmed death-ligand 1 induces effective natural killer cell responses against hepatocellular carcinoma. Wang Y, Li H, Liang Q, Liu B, Mei X, Ma Y. Tumour Biol. 36 1561-1566 (2015)
  20. RETRACTED: Silencing EGFR/HER3 signaling with a novel anti-EGFR domain II/IV antibody. Hu S, Dai H, Zhang T, Fu W, Berezov SD, Chen C, Jorissen D, Takeda H, Bethune AN. Cancer Lett. 357 374-383 (2015)
  21. Therapeutic TNF Inhibitors can Differentially Stabilize Trimeric TNF by Inhibiting Monomer Exchange. van Schie KA, Ooijevaar-de Heer P, Dijk L, Kruithof S, Wolbink G, Rispens T. Sci Rep 6 32747 (2016)