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

MAbs
Jenny FittingStefan Barth

Abstract

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 marrow biopsy specimens. We isolated the antibodies by phage display, using subtractive whole-cell panning with AML M2‑derived Kasumi‑1 cells. By selecting for internalizing scFv antibody fragments, we focused on potentially novel agents for intracellular drug delivery and tumor modulation. Two independent methods showed that 4 binders were internalized by Kasumi-1 cells. Furthermore, we observed the AML‑selective inhibition of cell proliferation and the induction of apoptosis by a recombinant immunotoxin comprising one scFv...Continue Reading

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Citations

Apr 13, 2017·Frontiers in Microbiology·Abdullah F U H SaeedShihua Wang
Jul 3, 2021·International Journal of Molecular Sciences·Byeongkwi MinYeup Yoon

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Methods Mentioned

BETA
phage display
ELISAs
ELISA
flow cytometry
confocal microscopy
transfection
biopsy
saturation-binding
protein assay
FACS

Software Mentioned

CellQuest
Windows Document Interface for
LEICA
GraphPad Prism
SWISS
Opera
MODEL
AIDA image analyzer
Vector NTI Advance 11 Sequence Analysis NTI AlignX
PyMOL

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