Apomab, a fully human agonistic DR5 monoclonal antibody inhibits tumour growth and osteolysis in murine models of breast cancer development and progression

Zinonos, Irene; Labrinidis, Agatha; Liapis, Vasilios; Hay, Shelley; Lee, Minjin; Ponomarev, V. E.; Diamond, Peter; Zannettino, Andrew C.W.; Findlay, D.; Evdokiou, Andreas

doi:10.1016/j.bone.2009.01.463

Cited by 3 publications

(6 citation statements)

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“…Cells were negative for mycoplasma using MycoAlert® Mycoplasma Detection Kit (Lonza, Basel, Switzerland). The generation of luciferase tagged H460 and A2780 cells was performed as described previously [35][36][37]. Chimeric DAB4 (chDAB4), resulting from the genetic fusion of the variable region sequences of murine DAB4 to the constant region sequences of human IgG1 (huIgG1) was created at CSIRO Manufacturing and produced using the CHO-XL99 system at the National Biologics Facility, Australian Institute for Bioengineering and Nanotechnology, University of Queensland (Queensland, Australia) [16,17].…”

Section: Cell Culture and Antibodiesmentioning

confidence: 99%

Positron Emission Tomographic Imaging of Tumor Cell Death Using Zirconium-89-Labeled APOMAB® Following Cisplatin Chemotherapy in Lung and Ovarian Cancer Xenograft Models

et al. 2021

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Purpose Early detection of tumor treatment responses represents an unmet clinical need with no approved noninvasive methods. DAB4, or its chimeric derivative, chDAB4 (APOMAB®) is an antibody that targets the Lupus associated antigen (La/SSB). La/SSB is over-expressed in malignancy and selectively targeted by chDAB4 in cancer cells dying from DNA-damaging treatment. Therefore, chDAB4 is a unique diagnostic tool that detects dead cancer cells and thus could distinguish between treatment responsive and nonresponsive patients. Procedures In clinically relevant tumor models, mice bearing subcutaneous xenografts of human ovarian or lung cancer cell lines or intraperitoneal ovarian cancer xenografts were untreated or given chemotherapy followed 24h later by chDAB4 radiolabeled with [89Zr]ZrIV. Tumor responses were monitored using bioluminescence imaging and caliper measurements. [89Zr]Zr-chDAB4 uptake in tumor and normal tissues was measured using an Albira SI Positron-Emission Tomography (PET) imager and its biodistribution was measured using a Hidex gamma-counter. Results Tumor uptake of [89Zr]Zr-chDAB4 was detected in untreated mice, and uptake significantly increased in both human lung and ovarian tumors after chemotherapy, but not in normal tissues. Conclusion Given that tumors, rather than normal tissues, were targeted after chemotherapy, these results support the clinical development of chDAB4 as a radiodiagnostic imaging agent and as a potential predictive marker of treatment response.

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Section: Cell Culture and Antibodiesmentioning

confidence: 99%

Positron Emission Tomographic Imaging of Tumor Cell Death Using Zirconium-89-Labeled APOMAB® Following Cisplatin Chemotherapy in Lung and Ovarian Cancer Xenograft Models

et al. 2021

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“…Presuming the receptors preferentially form homotrimers or even higher oligomers in the plasma membrane, it appears likely that aggregates higher than dimers would have been formed and detected in our cross-linking experiments. In fact, when we cross-linked soluble TNF with BS 3 , representing a homotrimer (3 ϫ 17 kDa) also containing 6 lysine residues per monomer, we readily detected a strong band of the supposed TNF homotrimer (data not shown). This indicates that an underes- FIGURE 7.…”

Section: Discussionmentioning

confidence: 99%

“…Cycloheximide and ␣-FLAG antibody (clone M2) were from Sigma. Bis(sulfosuccinimidyl)-suberate (BS 3 ) was purchased from Pierce. All chemicals were of analytical grade.…”

Section: Methodsmentioning

confidence: 99%

“…In the human system TRAIL binds four cell membrane receptors, TRAILR1 to TRAILR4, but also the soluble protein osteoprotegerin (2). Whereas the functional role of TRAIL interaction with osteoprotegerin is controversially discussed (3,4), the four membrane receptors fall into two classes. TRAILR1 and TRAILR2 each contain a cytoplasmic death domain (DD) and are thus capable to induce the cellular program of apoptosis but also anti-apoptotic signaling.…”

mentioning

confidence: 99%

“…The tumor necrosis factor superfamily member TNF-related apoptosis-inducing ligand (TRAIL) 3 has gained considerable interest in the scientific community during the past decades. This is mainly based on the findings that the ligand TRAIL has been shown to specifically induce apoptosis in many tumorderived cell lines or primary tumor cells, whereas most normal tissue cells are resistant to the apoptotic effects of TRAIL (1).…”

mentioning

confidence: 99%

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Dominant Negative Effects of Tumor Necrosis Factor (TNF)-related Apoptosis-inducing Ligand (TRAIL) Receptor 4 on TRAIL Receptor 1 Signaling by Formation of Heteromeric Complexes

Neumann

Hasenauer

Pollak

et al. 2014

Journal of Biological Chemistry

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Background:The mechanisms through which TRAILR4 interferes with proapoptotic signaling are not conclusively elucidated. Results: TRAILR4 forms ligand-independent heterodimers with TRAIL death receptors, thereby inhibiting both pro-and anti-apoptotic signaling. Conclusion: TRAILR4 exerts a dominant negative effect on TRAILR1 through the PLAD-mediated formation of mixed receptor complexes. Significance: Understanding the mechanism of TRAILR4-mediated apoptosis-inhibition can be advantageous for the development of new TRAIL receptor agonists for cancer therapy.

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An Fcγ Receptor-Dependent Mechanism Drives Antibody-Mediated Target-Receptor Signaling in Cancer Cells

et al. 2011

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Antibodies to cell-surface antigens trigger activatory Fcγ receptor (FcγR)-mediated retrograde signals in leukocytes to control immune effector functions. Here, we uncover an FcγR mechanism that drives antibody-dependent forward signaling in target cells. Agonistic antibodies to death receptor 5 (DR5) induce cancer-cell apoptosis and are in clinical trials; however, their mechanism of action in vivo is not fully defined. Interaction of the DR5-agonistic antibody drozitumab with leukocyte FcγRs promoted DR5-mediated tumor-cell apoptosis. Whereas the anti-CD20 antibody rituximab required activatory FcγRs for tumoricidal function, drozitumab was effective in the context of either activatory or inhibitory FcγRs. A CD40-agonistic antibody required similar FcγR interactions to stimulate nuclear factor-κB activity in B cells. Thus, FcγRs can drive antibody-mediated receptor signaling in target cells.

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Apomab, a fully human agonistic DR5 monoclonal antibody inhibits tumour growth and osteolysis in murine models of breast cancer development and progression

Cited by 3 publications

References 0 publications

Positron Emission Tomographic Imaging of Tumor Cell Death Using Zirconium-89-Labeled APOMAB® Following Cisplatin Chemotherapy in Lung and Ovarian Cancer Xenograft Models

Positron Emission Tomographic Imaging of Tumor Cell Death Using Zirconium-89-Labeled APOMAB® Following Cisplatin Chemotherapy in Lung and Ovarian Cancer Xenograft Models

Dominant Negative Effects of Tumor Necrosis Factor (TNF)-related Apoptosis-inducing Ligand (TRAIL) Receptor 4 on TRAIL Receptor 1 Signaling by Formation of Heteromeric Complexes

An Fcγ Receptor-Dependent Mechanism Drives Antibody-Mediated Target-Receptor Signaling in Cancer Cells

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