Current concepts in immunotherapy for the treatment of colorectal cancer.
Immunotherapy could have a role in the therapy of colorectal cancer as there is now convincing evidence that the immune system can specifically recognize and destroy malignant cells. The MAb 17-1A has been used in advanced and primary disease, along with newer agents such as anti-epidermal growth factor receptor (EGFR) antibody. Immunotherapy with autologous tumour cell vaccine, genetic modification of immunostimulatory cytokines, suicide genes and TAAs as discussed. The multiplicity of peptide and carbohydrate antigens which can be potential targets for immunotherapy are also discussed. These include MUC1, Thomsen-Friedenreich and Sialosyl-Tn antigens and HER2 / neu. Active specific immunotherapy with the anti-idiotypic antibodies CEAVac and 105AD7, along with DC vaccines, is being currently used in adjuvant clinical trials. 105AD7 has been shown to cause significantly greater apoptosis of tumour cells in colorectal cancer patients, while CEAVac generated T cell proliferative anti-CEA responses. Dendritic cells pulsed with tumour mRNA or TAAs currently are being assessed in clinical trials. The role of HSPs in the anti-tumour immune response is discussed. Non-specific immunotherapeutic agents used in clinical trials with chemotherapeutic regimens have not shown any definitive benefit. Tumour progression may occur as result of escape from the host anti-cancer immune response. Better understanding of mechanisms of tumour evasion could explain why immunotherapy trials in patients have not shown better results. These include down-regulation of immune responses by the tumour, altered expression of MHC and/or TAAs by tumour cells, altered expression of adhesion molecules by tumour and/or DCs and usurpation of the immune response to the advantage of the cancer.
Indar
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Division of Surgery, Queens Medical Centre, Nottingham, UK. Adrian.Indar@nottingham.ac.uk
Maxwell-Armstrong
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CA
Durrant
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LG
Carmichael
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Scholefield
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JH
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived; D019496:Cancer Vaccines / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000276:immunology / Q000628:therapy*; D003713:Dendritic Cells / Q000276:immunology; D006360:Heat-Shock Proteins / Q000502:physiology; D006801:Humans; D007111:Immunity, Cellular; D007167:Immunotherapy / Q000379:methods*; D051379:Mice
C405618:105AD7 antibody; D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D019496:Cancer Vaccines; D006360:Heat-Shock Proteins; C400149:Edrecolomab