Antitumor activity of a human cytotoxic T-cell line (TALL-104) in brain tumor xenografts

Malignant glioma in adults and primitive neuroectodermal tumors/medulloblas tomas in children are the most common malignant primary brain tumors that e ither respond poorly to current treatment or tend to recur. Adoptive therap y with TALL-104 cells-an IL-2-dependent, major histocompatibility complex n onrestricted, 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 administ ered TALL-104 cells and their efficacy in effecting survival of a rat model of human brain tumor. In vitro, TALL-104 cells showed significant cytotoxi c activity when added to human glioblastoma cell lines U-87 MC, U-251 MG, a nd A1690; the medulloblastoma cell lines DAOY, D283 Med, and D341 Med; and the epidermoid cancer cell line A431. In brain tumor-bearing rats, the amou nt of fluorescent dye-labeled TALL-104 cells in brain increased after they were given by intracarotid injection as compared with i.v. cell administrat ion. However, TALL-104 cells rapidly decreased to low levels within 1 h aft er intracarotid injection. This finding suggests that TALL-104 cells given systemically may not invade brain or tumor tissues, but rather may remain i n the vascular system, making this approach less efficient for brain tumor treatment. In a model of athymic rats engrafted with human A431 carcinoma b rain 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.