Antibody-based immunotherapeutic strategies in colorectal cancer

Monoclonal antibodies may well be on their way to becoming an integral part of therapy after the most recent success in prolonging overall and recurrence-free survival in patients with stage III colorectal cancer after potentially curative surgery. After a median follow-up of 5 years, antibody treatment reduced the overall death rate by 30% and decreased the recurrence rate by 27%. These results are similar with regard to efficacy but there is less toxicity with those obtained in contemporary and more recent chemotherapy trials. The key to success with high-molecular-weight substances such as immunoglobulines lies in the careful selection of the appropriate target population, i.e., patients with minimal residual disease, where only isolated tumor cells which are readily accessible to therapy are present. An argument for combining immunotherapy with chemotherapy can be made on the basis of the phenotype of individual disseminated tumor cells, which by immunocytochemistry were found to only rarely express proliferation-associated antigens and therefore are independent of the cell cycle. Further efforts to improve immunotherapy have also led to the combined clinical use of antibodies with biologic response modifiers which are known to enhance effector cell-mediated antibody-dependent cytotoxicity. Additional rationally designed clinical trials are ongoing in which specific immunotherapy is directed towards known, readily accessible, and abundant cell target structures, either alone or combined with treatment modalities which employ different action mechanisms.