The human leukemic T-cell line, TALL-104, is cytotoxic to human malignant brain tumors and traffics through brain tissue: Implications for local adoptive immunotherapy

Preclinical studies with the human MHC nonrestricted cytotoxic T-cell leuke mic line, TALL-104, were performed in anticipation of its use in cellular i mmunotherapy trials for primary malignant brain tumors. In this study, we h ave: (a) quantitated the irt vitro brain tumor cell lysis; (b) measured the cytokine secretion upon coincubation of TALL-104 cells with brain tumor ce lls; (c) investigated the effect of dexamethasone on brain tumor cell cytol ysis by TALL-104 cells; (d) explored the effects of lethal irradiation and cryopreservation on TALL-104 cell viability and lytic efficacy; and (e) est imated the damage TALL-104 cells induct: to murine normal and tumor brain c ells and their trafficking patterns in both normal and tumor-bearing rat br ain upon intracranial infusion. III vitro coincubation of TALL-104 cells wi th human brain tumor cells, explants, and cell lints resulted in significan t lysis of them, but normal brain cells were spared. Lysis of tumor at 4 h was unaffected by dexamethasone or lethal irradiation. Secretion of tumor n ecrosis factor-alpha, tumor necrosis fartor-beta, IFN-gamma, or granulocyte /macrophage-colony stimulating factor upon TALL-104 cell coincubation with brain tumor cells variably occurred without always correlating with lysis, In vivo experiments using irradiated TALL-104 cells, placed at multiple tim es into normal cannulated rat brain, produced focal sterile abscesses at th e instillation site hut no widespread allergic encephalitic reaction. Cells morphologically consistent with TALL-104 cells specifically trafficked fro m the site of instillation through the neuropil, occasionally into the cont ralateral brain, and egressed at perivascular and leptomeningeal spares, In vivo experiments with cannulated rats bearing 9L gliosarcoma showed a pref erential localization of the TALL-104 cells in tumor compared with normal b rain. Taken together, these data support the concept that TALL-104 cells ca n he used as a novel nontoxic and efficacious paradigm for cellular immunot herapy trials In human primary malignant brain tumors.