{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T03:33:23Z","timestamp":1790048003189,"version":"4.0.1"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2009,9,1]],"date-time":"2009-09-01T00:00:00Z","timestamp":1251763200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>CD97 is a member of the EGF-TM7 family of adhesion class receptors, with a proposed role in inflammatory cell recruitment. Neutralization of murine CD97 with the anti-mCD97 mAb 1B2 was efficacious in prevention of murine collagen-induced arthritis, a model with features resembling rheumatoid arthritis. Here, the therapeutic potential of neutralizing CD97 in arthritis was studied with emphasis on the 1B2 pharmacokinetics. Mice with established arthritis were treated with anti-mCD97 or anti-TNF-\u03b1 serum. Ab pharmacokinetics and biodistribution were studied in diseased and nondiseased mice using labeled 1B2. The impact of CD97 expression on Ab pharmacokinetics was studied using CD97 knockout mice. Treatment with 1B2 showed an efficacy comparable to anti-TNF-\u03b1 treatment. Pharmacokinetic analysis of 1B2 in wild-type and CD97 knockout mice indicated a dose-dependent Ab clearance, due to specific interaction with CD97. Biodistribution studies showed accumulation of 1B2 in spleen and lung. In vitro studies using murine splenocytes revealed that CD97 when bound to Ab was internalized. Moreover, soluble CD97 was detected in the supernatant, suggesting Ag shedding. Finally, in arthritic mice, higher levels of soluble CD97 were found and 1B2 treatment led to specific targeting of inflamed paws, resulting in a higher clearance rate of 1B2 in arthritic mice than in wild-type mice. In conclusion, our data support a therapeutic value of CD97 neutralization in experimental arthritis. The pharmacokinetic profile of the 1B2 Ab illustrates the complexity of Ab elimination from an organism and stresses the importance of understanding Ag-Ab interactions when developing therapeutic mAbs.<\/jats:p>","DOI":"10.4049\/jimmunol.0901253","type":"journal-article","created":{"date-parts":[[2009,8,28]],"date-time":"2009-08-28T20:44:23Z","timestamp":1251492263000},"page":"4127-4134","source":"Crossref","is-referenced-by-count":39,"title":["Therapeutic Antibody Targeting of CD97 in Experimental Arthritis: the Role of Antigen Expression, Shedding, and Internalization on the Pharmacokinetics of Anti-CD97 Monoclonal Antibody 1B2"],"prefix":"10.1093","volume":"183","author":[{"given":"Dorien M","family":"de Groot","sequence":"first","affiliation":[{"name":"Schering-Plough Research Institute , Oss,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerard","family":"Vogel","sequence":"additional","affiliation":[{"name":"Schering-Plough Research Institute , Oss,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Dulos","sequence":"additional","affiliation":[{"name":"Schering-Plough Research Institute , Oss,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonie","family":"Teeuwen","sequence":"additional","affiliation":[{"name":"Schering-Plough Research Institute , Oss,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Stebbins","sequence":"additional","affiliation":[{"name":"Schering-Plough Research Institute , Cambridge, MA 02143"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rg","family":"Hamann","sequence":"additional","affiliation":[{"name":"Department of Experimental Immunology, Academic Medical Center, University of Amsterdam , Amsterdam,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bronwyn M","family":"Owens","sequence":"additional","affiliation":[{"name":"Schering-Plough Research Institute , Cambridge, MA 02143"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"van Eenennaam","sequence":"additional","affiliation":[{"name":"Schering-Plough Research Institute , Oss,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ebo","family":"Bos","sequence":"additional","affiliation":[{"name":"Schering-Plough Research Institute , Oss,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annemieke M","family":"Boots","sequence":"additional","affiliation":[{"name":"Schering-Plough Research Institute , Oss,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,9,15]]},"reference":[{"key":"2026012811250917800_R1","first-page":"111","article-title":"Characterization of an early activation-dependent antigen on lymphocytes defined by the monoclonal antibody BL-Ac(F2).","volume-title":"Scand. 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Immunol.","year":"1996"},{"key":"2026012811250917800_R6","first-page":"439","article-title":"Molecular cloning and characterization of mouse CD97.","volume-title":"Int. Immunol.","year":"2000"},{"key":"2026012811250917800_R7","first-page":"303","article-title":"Structural characterization of mouse CD97 and study of its specific interaction with the murine decay-accelerating factor (DAF, CD55).","volume-title":"Immunology","year":"1999"},{"key":"2026012811250917800_R8","first-page":"1185","article-title":"The seven-span transmembrane receptor CD97 has a cellular ligand (CD55, DAF).","volume-title":"J. Exp. Med.","year":"1996"},{"key":"2026012811250917800_R9","first-page":"1701","article-title":"Characterization of the CD55 (DAF)-binding site on the seven-span transmembrane receptor CD97.","volume-title":"Eur. J. Immunol.","year":"1998"},{"key":"2026012811250917800_R10","first-page":"112","article-title":"Expression of the largest CD97 and EMR2 isoforms on leukocytes facilitates a specific interaction with chondroitin sulfate on B cells.","volume-title":"J. Leukocyte Biol.","year":"2005"},{"key":"2026012811250917800_R11","first-page":"2916","article-title":"The epidermal growth factor-like domains of the human EMR2 receptor mediate cell attachment through chondroitin sulfate glycosaminoglycans.","volume-title":"Blood","year":"2003"},{"key":"2026012811250917800_R12","first-page":"24160","article-title":"Molecular analysis of the epidermal growth factor-like short consensus repeat domain-mediated protein-protein interactions: dissection of the CD97-CD55 complex.","volume-title":"J. Biol. Chem.","year":"2001"},{"key":"2026012811250917800_R13","first-page":"1125","article-title":"The epidermal growth factor-seven transmembrane (EGF-TM7) receptor CD97 is required for neutrophil migration and host defense.","volume-title":"J. Immunol.","year":"2004"},{"key":"2026012811250917800_R14","first-page":"325","article-title":"Tissue distribution of the human CD97 EGF-TM7 receptor.","volume-title":"Tissue Antigens","year":"2001"},{"key":"2026012811250917800_R15","first-page":"6574","article-title":"Analysis of CD97 expression and manipulation: antibody treatment but not gene targeting curtails granulocyte migration.","volume-title":"J. Immunol.","year":"2008"},{"key":"2026012811250917800_R16","first-page":"R155","article-title":"CD97 neutralisation increases resistance to collagen-induced arthritis in mice.","volume-title":"Arthritis Res. Ther.","year":"2006"},{"key":"2026012811250917800_R17","first-page":"650","article-title":"Expression of the activation antigen CD97 and its ligand CD55 in rheumatoid synovial tissue.","volume-title":"Arthritis Rheum.","year":"1999"},{"key":"2026012811250917800_R18","first-page":"442","article-title":"Identification of the epidermal growth factor-TM7 receptor EMR2 and its ligand dermatan sulfate in rheumatoid synovial tissue.","volume-title":"Arthritis Rheum.","year":"2005"},{"key":"2026012811250917800_R19","first-page":"2645","article-title":"Antibody pharmacokinetics and pharmacodynamics.","volume-title":"J. Pharm. Sci.","year":"2004"},{"key":"2026012811250917800_R20","first-page":"81","article-title":"Elimination mechanisms of therapeutic monoclonal antibodies.","volume-title":"Drug Discov. Today","year":"2006"},{"key":"2026012811250917800_R21","first-page":"440","article-title":"The human EGF-TM7 receptor EMR3 is a marker for mature granulocytes.","volume-title":"J. Leukocyte Biol.","year":"2007"},{"key":"2026012811250917800_R22","first-page":"153","article-title":"A potent and selective p38 inhibitor protects against bone damage in murine collagen-induced arthritis: a comparison with neutralization of mouse TNF\u03b1.","volume-title":"Br. J. Pharmacol.","year":"2008"},{"key":"2026012811250917800_R23","first-page":"5049","article-title":"IL-1\u03b1\u03b2 blockade prevents cartilage and bone destruction in murine type II collagen-induced arthritis, whereas TNF-\u03b1 blockade only ameliorates joint inflammation.","volume-title":"J. Immunol.","year":"1999"},{"key":"2026012811250917800_R24","first-page":"2949","article-title":"Effectiveness of the soluble form of the interleukin-1 receptor accessory protein as an inhibitor of interleukin-1 in collagen-induced arthritis.","volume-title":"Arthritis Rheum.","year":"2003"},{"key":"2026012811250917800_R25","first-page":"3346","article-title":"Severity of murine collagen-induced arthritis correlates with increased CYP7B activity: enhancement of dehydroepiandrosterone metabolism by interleukin-1\u03b2.","volume-title":"Arthritis Rheum.","year":"2004"},{"key":"2026012811250917800_R26","first-page":"645","article-title":"Induction of tolerance with intranasal administration of human cartilage gp-39 in DBA\/1 mice: amelioration of clinical, histologic, and radiologic signs of type II collagen-induced arthritis.","volume-title":"Arthritis Rheum.","year":"2000"},{"key":"2026012811250917800_R27","first-page":"1052","article-title":"Enhancement of radiation dose to the nucleus by vesicular internalization of iodine-125-labeled A33 monoclonal antibody.","volume-title":"J. Nuclear Med.","year":"1996"},{"key":"2026012811250917800_R28","first-page":"1681","article-title":"Treatment of rheumatoid arthritis with chimeric monoclonal antibodies to tumor necrosis factor \u03b1.","volume-title":"Arthritis Rheum.","year":"1993"},{"key":"2026012811250917800_R29","first-page":"1051","article-title":"Sustained improvement over two years in physical function, structural damage, and signs and symptoms among patients with rheumatoid arthritis treated with infliximab and methotrexate.","volume-title":"Arthritis Rheum.","year":"2004"},{"key":"2026012811250917800_R30","first-page":"323","article-title":"TNF-\u03b1 neutralization in cytokine-driven diseases: a mathematical model to account for therapeutic success in rheumatoid arthritis but therapeutic failure in systemic inflammatory response syndrome.","volume-title":"Rheumatology (Oxford)","year":"2005"},{"key":"2026012811250917800_R31","first-page":"115","article-title":"The effects of circulating antigen on the pharmacokinetics and radioimmunoscintigraphic properties of 99m Tc labelled monoclonal antibodies in cancer patients.","volume-title":"J. Pharm. Pharm. Sci.","year":"1998"},{"key":"2026012811250917800_R32","first-page":"430","article-title":"BAI1 is an engulfment receptor for apoptotic cells upstream of the ELMO\/Dock180\/Rac module.","volume-title":"Nature","year":"2007"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/183\/6\/4127\/62695655\/9694.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/183\/6\/4127\/62695655\/9694.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T16:27:04Z","timestamp":1769617624000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/183\/6\/4127\/8053366"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,9]]},"references-count":32,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2009,9,15]]},"published-print":{"date-parts":[[2009,9,15]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.0901253","relation":{},"ISSN":["1550-6606","0022-1767"],"issn-type":[{"value":"1550-6606","type":"electronic"},{"value":"0022-1767","type":"print"}],"subject":[],"published-other":{"date-parts":[[2009,9]]},"published":{"date-parts":[[2009,9]]}}}