The role of immunotherapy in colorectal cancer

Despite landmark advances in the molecular biology and surgical adjuvant therapy of colorectal cancer in the past decade, this illness remains a significant health hazard. Conventional therapies, including surgery, radiation therapy, and chemotherapy, have had limited utility and have often resulted in unacceptable host toxicities. Therapies dependent on potentiation of the host immune response are attractive alternatives to conventional treatment because of their greater specificity and diminished toxicity. Furthermore, the efficacy of many of these therapies has been demonstrated in preclinical models, which is important given the relative refractoriness of colorectal cancer to chemotherapy. Both active specific therapies, such as tumor vaccines, and passive therapies, such as monoclonal antibodies, have been investigated. In early clinical trials, both have demonstrated modest activity. Nonspecific immune stimulation with agents such as bacillus Calmette-Guérin or methanol extraction residue appear to have little utility, but with the development of recombinant DNA technology, specific cytokines with more precisely identified targets have been synthesized in sufficient quantities for clinical trials. Finally, combinations of biologics or combinations of biologics with conventional therapies, such as fluorouracil (5-FU)/levamisole and 5-FU/interferon, have been investigated and appear to be useful in the treatment of surgically resected and advanced colorectal carcinoma, respectively. The utility of these therapies is hampered by a limited understanding of their precise mechanisms of action and optimal conditions for administration. Nevertheless, immunotherapy of colorectal carcinoma remains an important and promising area for further clinical investigation.