Apoptotic cell death induced by a mouse-human anti-APO-1 chimeric antibody leads to tumor regression

• Verfasst von: Coney, Leslie R. [VerfasserIn]
• Verfasst von: Daniel, Peter T. [VerfasserIn]
• Verfasst von: Sanborn, David [VerfasserIn]
• Verfasst von: Dhein, Jens [VerfasserIn]
• Verfasst von: Debatin, Klaus-Michael [VerfasserIn]
• Verfasst von: Krammer, Peter H. [VerfasserIn]
• Verfasst von: Zurawski Jr., V. R. [VerfasserIn]
• Titel: Apoptotic cell death induced by a mouse-human anti-APO-1 chimeric antibody leads to tumor regression
• Verf.angabe: Leslie R. Coney, Peter T. Daniel, David Sanborn, Jens Dhein, Klaus-Michael Debatin, Peter H. Krammer, V. R. Zurawski Jr.
• E-Jahr: 1994
• Jahr: 15 August 1994
• Umfang: 6 S.
• Fussnoten: Gesehen am 24.09.2024
• Titel Quelle: Enthalten in: International journal of cancer
• Ort Quelle: Bognor Regis : Wiley-Liss, 1966
• Jahr Quelle: 1994
• Band/Heft Quelle: 58(1994), 4, Seite 562-567
• ISSN Quelle: 1097-0215
• DOI: doi:10.1002/ijc.2910580419
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1903361257

Abstract

The murine anti-APO-1 antibody (γ3, k) induces programmed cell death (apoptosis) following binding to the APO-I antigen (m.w., 48 kDa) expressed, e.g., on activated or malignant lymphocytes. APO-I expression on malignant cell lines and tissues suggested potential clinical utility supported by anti-APO-I-mediated tumor regression in a nude mouse model. A mouse-human anti-APO-1 chimeric antibody (γ3, k) with an affinity similar to that of the murine antibody was produced. Chimeric anti-APO-1 showed the same potential to inhibit growth of the SKW6.4 B-lymphoblastoid cell line as murine anti-APO-1, In addition, both the chimeric and murine anti-APO-1 antibodies were equally capable of mediating complete macroscopic tumor regression of a SKW6.4 xenotransplant in SCID mice by induction of apoptosis. Induction of apoptosis was the only mechanism for tumor regression because neither murine nor chimeric anti-APO-1 showed anti-tumor activity against solid H53 tumor (APO-1 antigen-positive, anti-APO-1 -resistant) xenotransplants. Our results indicate that the chimeric anti-APO-1 antibody effectively induces apoptosis and suggest that chimeric anti-APO-1 should be evaluated for the treatment of malignant cells expressing the APO-1 antigen. However, chimeric anti-APO-1 might only be used therapeutically when the antibody can be targeted specifically to tumor cells.