Preclinical Changes in Immunoreactivity and Cellular Architecture during the Progressive Development of Intracranial Neoplasms and an Immunotherapeutic Schedule with a Novel Biological Response Modifier, the T11TS / S-LFA3.

Among neoplasms, brain tumors are particularly " difficult to treat" because of the partial immune privileged status of the brain and the presence of the blood brain barrier (Selmaj, 1996). Many details of progressive development of brain tumors remain unexplored and elucidation of consequent changes of the immune system with correlated cellular architecture and cell kinetics were the major objectives of the present course of investigations. Our studies have indicated that the primary resistance by the immune system to a growing tumor declines after a certain point, resulting in an immune suppressed state in a tumor bearing individual. The poor prognosis of malignant brain tumors with classical treatments like surgery, radiotherapy and chemotherapy has led to interest in immunotherapeutic protocols. In the present study, an attempt was made to determine the immunomodulatory and antitumor properties of a transmembrane glycopeptide of sheep red blood cells (SRBCs), known as S-LFA3 or T11TS. Young Druckray rat of both sexes aged 3-5 days were injected with N'-N'-ethyl nitrosourea (ENU) (i.p) to induce brain tumors and at 2,4,6,8 and 10 months of age were sacrificed for study of survival, tumor growth kinetics and immunological parameters like lymphocyte rosette formation, denoting CD2 - CD58 interactions and phagocytosis by peripheral macrophages and PMN hint at the changes during tumore development. In order to determine the immunomodulatory role of T11TS, 7 month old ENU induced animals and controls were injected with the compound (1 ml., i.p). The data obtained indicate that administration of T11TS results in increased survival of rats along with a decrease in growth kinetics of tumor cells to the normal level when compared to ENU induced animals of the same age. Pointers to mechanisms involving immunological investigations at the cellular level in these animals indicated improved lymphocyte function in terms of E-rosetting, augmented cytotoxicity and enhanced PMN and macrophage function in terms of phagocytosis. Finally histological examination showed complete reversal from the hyperplastic state to normal cellular homeostasis, indicating antitumor efficacy of T11TS, correlating very well with the data from survival and cell kinetic studies.