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Preclinical Experimental Therapeutics |
Children's Hospital of Philadelphia, Division of Neuro-oncology (B.G., C.-B.T., P.C.P.) and Department of Neurosurgery (S.M., L.N.S.), Philadelphia, PA 19104; and The Wistar Institute (A.C., S.V., D.S.), Hospital of the University of Pennsylvania, Department of Neurosurgery (K.D.J.), Philadelphia, PA 19104
2 Address correspondence and reprint requests to Peter C. Phillips, Children's Hospital of Philadelphia, Division of Neuro-Oncology, 3400 Civic Center Boulevard, Philadelphia, PA 19104.
Abstract
Malignant glioma in adults and primitive neuroectodermal tumors/medulloblastomas in children are the most common malignant primary brain tumors that either respond poorly to current treatment or tend to recur. Adoptive therapy with TALL-104 cells—an IL-2-dependent, major histocompatibility complex nonrestricted, cytotoxic T-cell line—has demonstrated significant antitumor activity against a broad range of implanted or spontaneously arising tumors. This study investigates distribution of systemically and locally administered TALL-104 cells and their efficacy in effecting survival of a rat model of human brain tumor. In vitro, TALL-104 cells showed significant cytotoxic activity when added to human glioblastoma cell lines U-87 MG, U-251 MG, and A1690; the medulloblastoma cell lines DAOY, D283 Med, and D341 Med; and the epidermoid cancer cell line A431. In brain tumor-bearing rats, the amount of fluorescent dye-labeled TALL-104 cells in brain increased after they were given by intracarotid injection as compared with i.v. cell administration. However, TALL-104 cells rapidly decreased to low levels within 1 h after intracarotid injection. This finding suggests that TALL-104 cells given systemically may not invade brain or tumor tissues, but rather may remain in the vascular system, making this approach less efficient for brain tumor treatment. In a model of athymic rats engrafted with human A431 carcinoma brain tumor, repetitive local administration of TALL-104 cells directly into the tumor bed resulted in a significant increase in survival time compared with control animals. Therefore, local therapy with TALL-104 cells may be a novel and highly effective treatment approach for malignant brain tumors.
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