Our hypothesis in this research program is that targeted passive immunity, employing autologous activated T cells (ATC), will permit the eradication of residual tumor cells, resulting in reduced rates of recurrence and extended survival in patients with malignant gliomas. The novelty of our approach is that we intend to circumvent the inherent limitation of lymphocyte clonality by starting with the patient’s own peripheral blood mononuclear cells (PBMC), polyclonally activating and expanding them in vitro and then arming them with bispecific antibodies (BiAbs) that will bypass the innate specificity of the T cell receptor (TCR) and target the entire population to antigen(s) uniquely expressed by the tumor cells. Polyclonal activation of PBMC in vitro has been shown to result in a population that is predominantly CD8+ cytotoxic T cells (CTL). BiAbs are prepared by chemical conjugation of OKT3 with a monoclonal antibody specific for a molecule expressed by the tumor cells. We will employ trastuzumab (Herceptin®), which binds to the HER2/neu molecule that is expressed on GBM, but not on non-malignant cells in the CNS. Thus, the OKT3 variable regions ensure arming of the CTL and the trastuzumab variable regions target the ATC to the tumor cells. We are currently developing a mouse xenograft model of glioblastoma that allows for systemic introduction of the armed ATCs, so that we can mimic a clinical treatment setting. This project is in collaboration with Lawrence Lum, MD, DSc, in the Depts. of Oncology, Medicine, and Immunology, WSU School of Medicine.