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

Neuro Oncol. 2000 Apr;2(2):103-13. doi: 10.1093/neuonc/2.2.103.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Brain Neoplasms / immunology
  • Brain Neoplasms / therapy*
  • Carcinoma / immunology
  • Carcinoma / therapy*
  • Carcinoma, Squamous Cell / immunology
  • Carcinoma, Squamous Cell / pathology
  • Carotid Arteries
  • Cytotoxicity, Immunologic
  • Glioblastoma / immunology
  • Glioblastoma / pathology*
  • Humans
  • Immunotherapy, Adoptive* / methods
  • Injections, Intra-Arterial
  • Injections, Intralesional
  • K562 Cells / immunology
  • K562 Cells / transplantation
  • Medulloblastoma / immunology
  • Medulloblastoma / pathology*
  • Neoplasm Transplantation
  • Rats
  • Rats, Nude
  • Stereotaxic Techniques
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Cytotoxic / radiation effects
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays