EPIDERMAL GROWTH FACTOR RECEPTOR AND G250: USEFUL TARGET ANTIGENS FOR ANTIBODY MEDIATED CELLULAR CYTOTOXICITY AGAINST RENAL CELL CARCINOMA?
2002; Lippincott Williams & Wilkins; Volume: 167; Issue: 2 Part 1 Linguagem: Inglês
10.1016/s0022-5347(01)69131-6
ISSN1527-3792
AutoresH. Stadick, Bernhard Stockmeyer, R.-B. Kühn, K. M. Schrott, J. R. Kalden, Martin J. Glennie, Jan G. J. van de Winkel, Martin Gramatzki, Thomas Valerius, D. ELS ̈ASSER,
Tópico(s)CAR-T cell therapy research
ResumoNo AccessJournal of UrologyINVESTIGATIVE UROLOGY1 Feb 2002EPIDERMAL GROWTH FACTOR RECEPTOR AND G250: USEFUL TARGET ANTIGENS FOR ANTIBODY MEDIATED CELLULAR CYTOTOXICITY AGAINST RENAL CELL CARCINOMA? H. STADICK, B. STOCKMEYER, R. KÜHN, K.M. SCHROTT, J.R. KALDEN, M.J. GLENNIE, J.G.J. van de WINKEL, M. GRAMATZKI, T. VALERIUS, and D. ELS¨ASSER H. STADICKH. STADICK More articles by this author , B. STOCKMEYERB. STOCKMEYER More articles by this author , R. KÜHNR. KÜHN More articles by this author , K.M. SCHROTTK.M. SCHROTT More articles by this author , J.R. KALDENJ.R. KALDEN More articles by this author , M.J. GLENNIEM.J. GLENNIE More articles by this author , J.G.J. van de WINKELJ.G.J. van de WINKEL Statistically significant More articles by this author , M. GRAMATZKIM. GRAMATZKI More articles by this author , T. VALERIUST. VALERIUS More articles by this author , and D. ELS¨ASSERD. ELS¨ASSER More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(01)69131-6AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Monoclonal antibodies are a novel treatment option for certain tumor patients. We evaluated the potential of antibody derivatives against epidermal growth factor receptor and G250, which are 2 candidate antigens on renal cell carcinoma, to recruit effector cells for killing renal cell carcinoma. Material and Methods: As a measure of cytotoxicity, 51chromium release assays against renal cell carcinoma lines were performed using unseparated blood or isolated cell populations as the source of effectors. Blood was obtained from healthy donors, or from patients receiving granulocyte-macrophage colony-stimulating factor or granulocyte colony-stimulating factor for enhancing effector cell function. Parental human IgG1 antibodies against epidermal growth factor receptor and G250 were compared with respective chemically linked bispecific antibodies targeting IgA Fc receptor FcαRI (CD89), a novel cytotoxic trigger molecule on polymorphonuclear cells and monocytes/macrophages, which were constructed by chemically crosslinking appropriate F(ab′) fragments. Results: Renal cell carcinoma lines were highly resistant to complement dependent lysis. With mononuclear effector cells high levels of renal cell carcinoma killing were observed with a humanized epidermal growth factor receptor directed monoclonal antibody, while the same antibody did not recruit granulocytes (polymorphonuclear cells) for antibody dependent cell mediated cytotoxicity. However, polymorphonuclear cells effectively lysed renal cell carcinoma with [FcαRI × epidermal growth factor receptor] bispecific antibody. FcαRI mediated killing was significantly enhanced when the blood of patients on granulocyte colony-stimulating factor or granulocyte-macrophage colony-stimulating factor therapy was analyzed. However, G250 mediated only low levels of killing with mononuclear cell but not with polymorphonuclear effector cells. Conclusions: Targeting epidermal growth factor receptor proved to recruit efficiently mononuclear or polymorphonuclear cell mediated killing mechanisms, while G250 directed antibody constructs were significantly less effective. Particularly effective renal cell carcinoma killing was observed with combined [FcαRI × epidermal growth factor receptor] bispecific antibody and granulocyte colony-stimulating factor or granulocyte-macrophage colony-stimulating factor. References 1 : Systemic therapy for renal cell carcinoma. J Urol2000; 163: 408. Link, Google Scholar 2 : Unconjugated monoclonal antibodies for the treatment of hematologic and solid malignancies. 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Google Scholar 34 : Therapeutic efficacy of FcγRI/CD64-directed bispecific antibodies in B-cell lymphoma. Blood2000; 96: 3544. Google Scholar From the Departments of Medicine III and Urology, University of Erlangen-Nürnberg, Erlangen, Germany, Tenovus Research Laboratory, University of Southampton, Southampton, United Kingdom, and Immunotherapy Laboratory, Department of Immunology, University Medical Center Utrecht and Genmab, Utrecht, The Netherlands© 2002 by American Urological Association, Inc.FiguresReferencesRelatedDetails Volume 167Issue 2 Part 1February 2002Page: 707-712 Advertisement Copyright & Permissions© 2002 by American Urological Association, Inc.Keywordsreceptors, Fccarcinoma, renal callantibody-dependent cell cytotoxicityimmunotherapykidneyMetricsAuthor Information H. STADICK More articles by this author B. STOCKMEYER More articles by this author R. KÜHN More articles by this author K.M. SCHROTT More articles by this author J.R. KALDEN More articles by this author M.J. GLENNIE More articles by this author J.G.J. van de WINKEL Statistically significant More articles by this author M. GRAMATZKI More articles by this author T. VALERIUS More articles by this author D. ELS¨ASSER More articles by this author Expand All Advertisement PDF DownloadLoading ...
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