Bio-immunotherapy for cancer in experimental studies and clinical application: current status and future challenges

Although successful treatment of patients with primary tumor by conventional surgery and radiotherapy is often possible, death frequently results from tumor metastases. Since metastasis has already occurred in many cancer patients at the time of diagnosis, a major emphasis of cancer treatment is and will continue to be the prevention or successful management of tumor metastases. Systemic chemotherapy has been widely used in the past in the hope of preventing or controlling micrometastases. The results of this treatment have been disappointing with little impact on survival in the vast majority of solid tumors. Bio-immunotherapy has emerged as another modality and is finding acceptance and use in treating patients with cancer. The role of bio-immunotherapy in traditional surgery, radiotherapy, chemotherapy and hyperthermia will be discussed. In order to evaluate new and innovative treatments, we and others have used murine models of erythroleukemia and solid tumors with metastatic potential to assess the effects in vivo of bio-immunotherapy. Tumor metastases can be dampened and immunosuppression restored by bio-immunotherapy, especially when used in combination with other forms of treatment. Most of the combination treatments used in animal models are encouraging but are by no means totally adequate or curative yet. The molecular basis of cancer is now understood to involve activation of dominant oncogenes and inactivation of tumor suppressor genes. These genetic events may represent novel targets for cancer treatment. The potential use and ethical implications of gene transfer to alter the behavior of somatic cells in patients with cancer has been noted. Also reported is genetic immunomodulation by introducting genes for cytokines into tumor cells or lymphocytes to stimulate a cytotoxic immune response against the tumor. As with bone marrow, human cord blood can be used for transplantation in the autologous, related allogeneic and unrelated allogeneic settings, and as a target cell for gene treatment. It is believed that the greatest therapeutic results of bio-immunotherapy, including biological response modifiers, cytokines, gene treatment and bone marrow transplantation, will come in combination with other established effective modalities including surgery, radiation treatment, chemotherapy and hyperthermia in the treatment of patients with cancer.