Reversal of acute myelogenous leukemia in humanized SCID mice using a novel adoptive transfer approach.
Advanced human malignancies cannot be permanently cured by adoptive transfer of autologous lymphokine-activated killer (LAK) cells. Moreover, administration of high doses of IL-2 to maintain LAK activity in vivo is associated with severe toxicity. In this study, we tested the anti-tumor efficacy of a uniquely potent MHC non-restricted human killer T cell clone (TALL-104) in humanized severe combined immunodeficient (SCID) mice bearing acute myelogenous leukemia (AML). We show that, in appropriate experimental conditions, TALL-104 cells could effectively reverse the aggressive growth of the myelomonocytic leukemia cell line U937 in SCID mouse tissues, leading to complete abrogation of AML. A single transfer of TALL-104 cells at the time of tumor challenge in combination with recombinant human (rh) IL-12 (1 microgram/d) prolonged significantly the life of the mice. However, eradication of leukemia, as monitored both clinically and by PCR, was achieved by repeated injection of the effectors at close intervals. Complete cure was obtained also upon transfer of lethally irradiated (non-proliferating) TALL-104 cells together with low doses of rh IL-2 (100 U/d). Most notably, of the mice that received multiple transfers of TALL-104 cells without cytokines in an advanced disease stage, 50% were clinically cured, and 50% survived significantly longer. The potential of TALL-104 cells as an effective and safe leukemia purging agent is discussed.
Cesano
A
A
Wistar Institute of Anatomy and Biology, Philadelphia, Pennsylvania 19104.
Visonneau
S
S
Cioé
L
L
Clark
S C
SC
Rovera
G
G
Santoli
D
D
D000818:Animals; D002460:Cell Line; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D005047:Etoposide / Q000627:therapeutic use; D005720:Gamma Rays; D006801:Humans; D007165:Immunosuppression Therapy; D016219:Immunotherapy, Adoptive; D015979:Killer Cells, Lymphokine-Activated; D007694:Killer Cells, Natural / Q000276:immunology / Q000528:radiation effects; D015470:Leukemia, Myeloid, Acute / Q000628:therapy*; D017710:Lymphocyte Transfusion; D051379:Mice; D016513:Mice, SCID; D016133:Polymerase Chain Reaction; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D005047:Etoposide