Abstract
The number of anti-cancer antibodies in therapy and in clinical trials is increasing gradually while their curative efficacy remains rather limited due to the resistance of tumor cells to complement-dependent cytotoxicity (CDC). An updated review of the various defense mechanisms complement is confronting when tackling a tumor cell is presented. The mechanisms discussed are: membrane and secreted complement regulatory proteins, heat shock proteins, extracellular proteases and protein kinases, cell surface sialylation and intracellular survival anti-lytic signals. Projected treatment strategies are depicted for each of the complement resistance mechanisms. It is conceivable that the therapeutic capacity of anti-cancer antibodies will be amplified once combined with a reagent that sensitizes the cancer cells to CDC.
MeSH terms
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Animals
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Antibodies / therapeutic use*
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Antibody-Dependent Cell Cytotoxicity / immunology*
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C-Reactive Protein / immunology
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C-Reactive Protein / metabolism
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CD55 Antigens / immunology
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CD55 Antigens / metabolism
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CD59 Antigens / immunology
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CD59 Antigens / metabolism
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Complement System Proteins / immunology*
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Complement System Proteins / metabolism
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HSC70 Heat-Shock Proteins / immunology
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HSC70 Heat-Shock Proteins / metabolism
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HSP90 Heat-Shock Proteins / immunology
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HSP90 Heat-Shock Proteins / metabolism
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Humans
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Membrane Cofactor Protein / immunology
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Membrane Cofactor Protein / metabolism
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Neoplasms / immunology*
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Neoplasms / therapy*
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Peptide Hydrolases / immunology
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Peptide Hydrolases / metabolism
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Protein Kinases / immunology
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Protein Kinases / metabolism
Substances
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Antibodies
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CD55 Antigens
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CD59 Antigens
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HSC70 Heat-Shock Proteins
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HSP90 Heat-Shock Proteins
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Membrane Cofactor Protein
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Complement System Proteins
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C-Reactive Protein
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Protein Kinases
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Peptide Hydrolases