Abstract
The potential for disease-specific targeting and low toxicity profiles have made monoclonal antibodies attractive therapeutic drug candidates. Antibody-mediated target cell killing is frequently associated with immune effector mechanisms such as antibody-directed cellular cytotoxicity, but they can also be induced by apoptotic processes. Antibody-directed mechanisms, including antigen crosslinking, activation of death receptors, and blockade of ligand-receptor growth or survival pathways, can elicit the induction of apoptosis in targeted cells. Depending on their mechanism of action, monoclonal antibodies can induce targeted cell-specific killing alone or can enhance target cell susceptibility to chemo- or radiotherapeutics by effecting the modulation of antiapoptotic pathways. This review will focus on the mechanisms by which antibodies are capable of eliciting programmed cell death either directly or indirectly within tumor cells.
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Abbreviations
- ADCC:
-
antibody-dependent cellular cytotoxicity
- CDC:
-
complement-dependent cellular cytotoxicity
- IAP:
-
inhibitor of apoptosis
- RTK:
-
receptor tyrosine kinase
- TNFR:
-
tumor necrosis factor receptor
- TRAIL:
-
TNF-related apoptosis-inducing ligand receptor
- EGFR:
-
epidermal growth factor receptor
- IGF-1R:
-
insulin-like growth factor-1 receptor
- FGFR:
-
fibroblast growth factor receptor
- PDGFR:
-
platelet-derived growth factor receptor
- VEGF:
-
vascular endothelial growth factor
- PI3K:
-
phosphoinositol 3-kinase
- PLCγ:
-
phospholipase C gamma
- MAPK:
-
mitogen-activated protein kinase
- TGF-α:
-
transforming growth factor-α
- IR:
-
ionizing radiation
- SCCHN:
-
squamous cell carcinoma of the head and neck
- DNA-PK:
-
DNA-dependent protein kinase
- JNK:
-
c-jun N-terminal protein kinase
- NHL:
-
non-Hodgkin's lymphoma
- AML:
-
acute myelogenous leukemia
- CLL:
-
chronic lymphocytic leukemia
- ADEPT:
-
antibody-directed enzyme prodrug therapy
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Ludwig, D., Pereira, D., Zhu, Z. et al. Monoclonal antibody therapeutics and apoptosis. Oncogene 22, 9097–9106 (2003). https://doi.org/10.1038/sj.onc.1207104
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