Treatment of experimental glioblastoma with a human major histocompatibility complex nonrestricted cytotoxic T cell line.
This study investigates a new approach to adoptive therapy of glioblastoma using as antitumor effector a potent major histocompatibility complex nonrestricted killer clone (TALL-104) established from a patient with acute T-lymphoblastic leukemia. The human glioblastoma cell line U-87 MG could be successfully engrafted in mice with severe combined immunodeficiency using the i.p., intracerebral, and s.c. routes. The latter model was elected to evaluate therapy based on its high reproducibility. Tumor growth in mice engrafted s.c. was proportionally associated with splenomegaly and leukocytosis. Multiple transfers of lethally irradiated (non-proliferating) TALL-104 cells at the tumor site resulted in about 50-70% inhibition of tumor growth as compared to untreated mice, with concomitant reduction of splenomegaly and leukocytosis. The antitumor effects were inversely proportional to the size of the tumor at initiation of therapy, 90-100% inhibition occurring in severe combined immunodeficiency mice treated from the day of U-87 MG challenge. Neither splenomegaly nor leukocytosis developed in animals in which tumor growth was completely blocked. Stimulation of TALL-104 cells with either interleukin 2 or interleukin 12 prior to irradiation and adoptive transfer increased the antitumor efficacy of the killer cells to about the same extent. The potential usefulness of irradiated TALL-104 cells in adjuvant therapy against glioblastomas and other well-localized tumors is discussed.
Cesano
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Wistar Institute of Anatomy and Biology, Philadelphia, Pennsylvania 19104.
Visonneau
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Santoli
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D000818:Animals; D002999:Clone Cells; D005909:Glioblastoma / Q000473:pathology / Q000628:therapy*; D016219:Immunotherapy, Adoptive; D018664:Interleukin-12 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D007964:Leukocytosis; D051379:Mice; D016513:Mice, SCID; D013163:Splenomegaly; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000528:radiation effects
D007376:Interleukin-2; D018664:Interleukin-12