Details

Autor(en) / Beteiligte

• STADICK, H.
• STOCKMEYER, B.
• KÜHN, R.
• SCHROTT, K.M.
• KALDEN, J.R.
• GLENNIE, M.J.
• van de WINKEL, J.G.J.
• GRAMATZKI, M.
• VALERIUS, T.
• ELS¨ASSER, D.

Titel

EPIDERMAL GROWTH FACTOR RECEPTOR AND G250: USEFUL TARGET ANTIGENS FOR ANTIBODY MEDIATED CELLULAR CYTOTOXICITY AGAINST RENAL CELL CARCINOMA?

Ist Teil von

• The Journal of urology, 2002-02, Vol.167 (2), p.707-712

Ort / Verlag

Hagerstown, MD: Elsevier Inc

Erscheinungsjahr

2002

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. 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. 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. 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.