Monoclonal antibodies as therapeutic tools in cancer

Monoclonal antibodies were derived more than 20 years ago, but only now the available results from clinical studies suggest the promise of antibody-based therapy of cancer. The emergence of drug-resistant tumor cells and the insufficient tumor selectivity of conventional chemotherapy, encouraged research to reconsider the targeting properties of the immune system to improve the selectivity of anti-tumor therapy. The application of molecular biology technology allowed improving the quality of antibody by decreasing the size and producing humanized or even totally human reagents. These new generations af antibodies show improved tumor penetration and a reduced induction of human antimouse antibody response that impaired repetitive use of antibodies of first generation. The humanized form of and anti-CD20 monoclonal antibody (Rituxan) represents the first antibody approved by the FDA for therapeutic use in cancer. Forty-seven percent of the patients with low-grade lymphoma resistant to chemotherapy, showed objective response after Rituxan treatment. The other commercially available antibody approved in Germany for use in colon cancer is the 17-1A used as adjuvant therapy for patients with Duke's C colon cancer following resection. In this study, improved survival was observed in antibody treated patients with minimal residual disease, instead of advanced disease, with a 30% reduction in death and a 27% reduction in recurrence. The antigen characteristics, as well as the site of the disease play a significant role in determining success of antibody treatment. It is the case of stage III ovarian cancer patients treated intraperitoneally with autologous lymphocytes redirected to the tumor by an antibody recognizing both the tumor cells and the lymphocytes. In this case both arms of the immune system are used against cancer. The overall response was 27%, with long lasting complete responses. Antibodies can be uses also as immunoconjugates to provide targeting specificity to cytotoxic moieties like catalytic toxins, chemotherapeutic agents and radionuclides. Promising results were obtained with all these molecules. Full exploitation of antibody-based cancer therapy will probably depends on the adopted strategies, in particular a productive use of antibody could be as supplement to existing therapies and their application for patients with minimal residual disease instead of large tumor masses.