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

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-A...

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Hauptverfasser: Coney, Leslie R. (VerfasserIn) , Daniel, Peter T. (VerfasserIn) , Sanborn, David (VerfasserIn) , Dhein, Jens (VerfasserIn) , Debatin, Klaus-Michael (VerfasserIn) , Krammer, Peter H. (VerfasserIn) , Zurawski Jr., V. R. (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 15 August 1994
In: International journal of cancer
Year: 1994, Jahrgang: 58, Heft: 4, Pages: 562-567
ISSN:1097-0215
DOI:10.1002/ijc.2910580419
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1002/ijc.2910580419
Verlag, lizenzpflichtig, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/ijc.2910580419
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Verfasserangaben:Leslie R. Coney, Peter T. Daniel, David Sanborn, Jens Dhein, Klaus-Michael Debatin, Peter H. Krammer, V. R. Zurawski Jr.

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520 |a 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. 
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