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Phage display-based generation of novel internalizing antibody fragments for immunotoxin-based treatment of acute myeloid leukemia.

MAbs. . 2015-04;  7(2):390-402
Fitting J, Blume T, Ten Haaf A, Blau W, Gattenlöhner S, Tur MK, Barth S. Department of Experimental Medicine and Immunotherapy; Institute of Applied Medical Engineering; Helmholtz-Institute for Biomedical Engineering ; University Hospital RWTH Aachen ; Aachen , Germany.
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摘要

The current standard treatment for acute myeloid leukemia (AML) is chemotherapy based on cytarabine and daunorubicine (7 + 3), but it discriminates poorly between malignant and benign cells. Dose-limiting off target effects and intrinsic drug resistance result in the inefficient eradication of leukemic blast cells and their survival beyond remission. This minimal residual disease is the major cause of relapse and is responsible for a 5-year survival rate of only 24%. More specific and efficient approaches are therefore required to eradicate malignant cells while leaving healthy cells unaffected. In this study, we generated scFv antibodies that bind specifically to the surface of AML blast cells and AML bone mar... More

关键词

AML immunohistochemistry; AML; acute myeloid leukemia; CDR; Complementarity Determining Region; ETA; Pseudomonas exotoxin A; PBMC; peripheral blood mononuclear cell; acute myeloid leukemia; anti-AML antibody fragments; in vitro efficacy; internalizing phage antibodies; phage display technology; primary AML blast cells; recombinant immunotoxin; scFv; single chain variable fragment