Lonely killers: Effector cell- and complement-independent non-proapoptotic cytotoxic antibodies inducing membrane lesions

The majority of the most effective monoclonal antibodies (mAbs) currently in the clinics bind to cancer or immune cells. Classic mechanisms of cell killing by therapeutic mAbs include antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity and induction of apoptosis by engag...

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Bibliographic Details
Published in:mAbs 2011-11, Vol.3 (6), p.528-534
Main Authors: Fernández-Marrero, Yuniel, López-Requena, Alejandro
Format: Article
Language:English
Subjects:
Animals
Antibodies, Monoclonal - immunology
Antibodies, Monoclonal - therapeutic use
Antibodies, Neoplasm - immunology
Antibodies, Neoplasm - therapeutic use
Antibody-Dependent Cell Cytotoxicity
Antigens, Neoplasm - immunology
Binding
Biology
Bioscience
Calcium
Cancer
Cell
Cell Membrane - immunology
Cell Membrane - pathology
Cycle
G(M3) Ganglioside - analogs & derivatives
G(M3) Ganglioside - immunology
Humans
Immunotherapy
Landes
Mice
Neoplasms - immunology
Neoplasms - therapy
Organogenesis
Proteins
Review
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Summary:The majority of the most effective monoclonal antibodies (mAbs) currently in the clinics bind to cancer or immune cells. Classic mechanisms of cell killing by therapeutic mAbs include antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity and induction of apoptosis by engagement of specific cell ligands. A few reports have described mAbs whose cytotoxic activity is Fc-independent and that do not induce the morphological and biochemical changes associated with the apoptosis-type of cell death. Even fewer works describe mAbs able to directly induce membrane lesions. Here, we discuss the available data on those molecules and their cell killing activity, with particular attention to the case of a mAb specific for the tumor-associated N-glycolyl (Neu5Gc)-GM3 ganglioside (GM3(Neu5Gc)). Some similarities are found in the cell death pathways triggered by these mAbs, but data are not abundant. We conclude that the usefulness of mAbs with a direct cytotoxic activity for immunotherapeutic strategies deserves deeper research.
ISSN:1942-0862
1942-0870
DOI:10.4161/mabs.3.6.17770