Antitumor activity of a human cytotoxic T-cell line (TALL-104) in brain tumor xenografts.
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.
Geoerger
B
B
Children's Hospital of Philadelphia, Division of Neuro-oncology, PA 19104, USA.
Tang
C B
CB
Cesano
A
A
Visonneau
S
S
Marwaha
S
S
Judy
K D
KD
Sutton
L N
LN
Santoli
D
D
Phillips
P C
PC
D000818:Animals; D001932:Brain Neoplasms / Q000276:immunology / Q000628:therapy*; D002277:Carcinoma / Q000276:immunology / Q000628:therapy*; D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000473:pathology; D002339:Carotid Arteries; D003602:Cytotoxicity, Immunologic; D005909:Glioblastoma / Q000276:immunology / Q000473:pathology*; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods; D007269:Injections, Intra-Arterial; D015552:Injections, Intralesional; D020014:K562 Cells / Q000276:immunology / Q000637:transplantation; D008527:Medulloblastoma / Q000276:immunology / Q000473:pathology*; D009368:Neoplasm Transplantation; D051381:Rats; D011923:Rats, Nude; D013238:Stereotaxic Techniques; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000528:radiation effects; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays