Aspects of immunobiology and immunotherapy and uses of monoclonal antibodies and biologic immune modifiers in human gliomas.

Recent progress in brain tumor biology research has helped us to understand the causes of our failure to improve patient survival with current therapeutic approaches. Present combination regimens of surgery, radiotherapy, and chemotherapy fail to address adequately two inherent biologic properties of brain tumors: tumor-induced host immunosuppression and tumor cell heterogeneity. Future success in immunotherapy will depend on our ability to dissect the mechanisms involved in tumor-host interactions. Also, therapies may have to be individualized. The potential for MAs in research and clinical application is great owing to their unlimited discriminative power for molecular and functional characterization. Differential diagnosis of difficult cases, such as parenchymatous tumors or neoplastic cells in CSF, with panels of MAs will be available in the near future. The use of MAs to direct localization and therapy of brain tumors is also promising, as evidenced by the preliminary data from our laboratory and from those of other workers. Other applications of MAs, such as prevention of invasion and metastasis by targeting cell surface molecules involved in cell-matrix attachment function, are also under study. Future refinement in MA-specificity and in enhancement of MA-delivery to tumor sites will significantly complement new therapeutic approaches. As brain tumors evade immunosurveillance through active participation in inducing tumor-specific immunosuppression, successful immunotherapy, either passive serotherapy or active immunization, will be best achieved in patients with a slight or moderate immunosuppressive state. Alteration of immune status with various biologic response modifiers to boost host reactivity against tumors will be an important adjunct in our arsenal against brain tumors. IFNs, with their direct tumoricidal activity, and lymphokines (such as interleukin-2) may be such reagents with a promising future.