apomab?, a la-specific monoclonal antibody, detects the apoptotic tumor response to life-prolonging and dna-damaging chemotherapyapomab ,la-specific单克隆抗体,检测凋亡的肿瘤反应延长生命,能损伤dna的化疗.pdf
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APOMABH, a La-Specific Monoclonal Antibody, Detects
the Apoptotic Tumor Response to Life-Prolonging and
DNA-Damaging Chemotherapy
1 1 2 2 3 1,4
Fares Al-Ejeh , Jocelyn M. Darby , Chris Tsopelas , Douglas Smyth , Jim Manavis , Michael P. Brown *
1 Experimental Therapeutics Laboratory, Hanson Institute, Adelaide, South Australia, Australia, 2 Department of Nuclear Medicine, Royal Adelaide Hospital, Adelaide,
South Australia, Australia, 3 Centre for Neurological Disease, Hanson Institute, Adelaide, South Australia, Australia, 4 Department of Medical Oncology, Royal Adelaide
Hospital Cancer Centre and School of Medicine, The University of Adelaide, Adelaide, South Australia, Australia
Abstract
Background: Antineoplastic therapy may impair the survival of malignant cells to produce cell death. Consequently, direct
measurement of tumor cell death in vivo is a highly desirable component of therapy response monitoring. We have
previously shown that APOMABH representing the DAB4 clone of a La/SSB-specific murine monoclonal autoantibody is a
malignant cell-death ligand, which accumulates preferentially in tumors in an antigen-specific and dose-dependent manner
after DNA-damaging chemotherapy. Here, we aim to image tumor uptake of APOMABH (DAB4) and to define its biological
correlates.
Methodology/Principal Findings: Brisk tumor cell apoptosis is induced in the syngeneic EL4 lymphoma model after
treatment of tumor-bearing mice with DNA-damaging cyclophosphamide/etoposide chemotherapy. Tumor and normal
organ accumulation of Indium 111 (111In)-labeled La-specific DAB4 mAb as whole IgG or IgG fragments was quantified by
whole-body static im
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