Brain tumors of glial origin i.e. glioma are most difficult neoplasm to treat with modern therapeutic interventions viz. surgery, radio- and chemotherapies. Therefore, a continuous search is ‘on’ for the alternative modalities of treatment particularly with different immunomolecular therapeutic regimes. Use of restorative and adaptive immunotherapies with different BRMs, cytokines, tumor vaccines, site directed therapies with molecular blocking agents are now practiced to combat with glioma and still no major breakthrough has been obtained to extend life expectancy significantly. In our laboratory a novel immunotherapeutic probe i.e. T11TS/SLFA3, a membrane glycoprotein of sheep erythrocyte, with its activities of glioma killing in experimental animals has been attempted. With the fundamental details of neuroimmune components, particularly the resident microglia and brain infiltrating lymphocytes, the modulation of their activities by T11TS was evidenced. The activation of microglia, infiltration of lymphocytes, enhanced performance of effector functions and regulation of the cytokine network with T11TS in the brain compartment superseding the glioma induced immune suppression, is the major achievement found with T11TS mediated immunotherapy. These immune effector functions are culminated into the clearance of glioma, which is clearly depicted by the study of apoptosis and cell cycle analysis. This molecule with the carnage of glioma differentially regulates the population of microglia and lymphocytes in brain to regain homeostasis by modulating intrinsic cellular protein levels. Additionally, when this glycoprotein is used for toxicological evaluation, it showed mearly no adverse effects on animals, rather health promotion. Therefore, this glycoprotein T11TS potentially provides an effective immunotherapeutic option against glioma with the potentials of new drug development.