Cancer resistance to complement-dependent cytotoxicity (CDC): Problem-oriented research and development.
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.
Gancz
Dana
D
Department of Cell and Developmental Biology, Tel Aviv University, Israel.
Fishelson
Zvi
Z
D000818:Animals; D000906:Antibodies / Q000627:therapeutic use*; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology*; D002097:C-Reactive Protein / Q000276:immunology / Q000378:metabolism; D018958:CD55 Antigens / Q000276:immunology / Q000378:metabolism; D018957:CD59 Antigens / Q000276:immunology / Q000378:metabolism; D003165:Complement System Proteins / Q000276:immunology* / Q000378:metabolism; D050883:HSC70 Heat-Shock Proteins / Q000276:immunology / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000276:immunology / Q000378:metabolism; D006801:Humans; D051916:Membrane Cofactor Protein / Q000276:immunology / Q000378:metabolism; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*; D010447:Peptide Hydrolases / Q000276:immunology / Q000378:metabolism; D011494:Protein Kinases / Q000276:immunology / Q000378:metabolism
D000906:Antibodies; D018958:CD55 Antigens; D018957:CD59 Antigens; D050883:HSC70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D051916:Membrane Cofactor Protein; D003165:Complement System Proteins; D002097:C-Reactive Protein; D011494:Protein Kinases; D010447:Peptide Hydrolases