| Abstract: |
Efforts to limit GVHD mediated by alloreactive donor T cells after allogeneic bone marrow transplantation are limited by a concomitant decrease in graft-versus-tumor (GVT) activity and increased possibilities of tumor relapse. Using a novel approach, we adoptively transferred conventional T cells expressing the transcription factor promyelocytic leukemia zinc finger (PLZF), which confers effector properties resembling invariant natural killer T cells, such as copious production of cytokines under suboptimal stimulation. PLZF expression in T-cell allografts attenuates expansion of alloreactive T cells, leading to lower GVHD. Intact alloreactivity-driven antitumor cytokine responses result in preserved GVT effects, leading to improved survival. Our findings suggest that therapy with PLZF-overexpressing T cells would result in overall improved outcomes due to less GVHD and intact GVT effects. © 2013 American Association for Cancer Research. |
| Keywords: |
controlled study; protein expression; survival rate; transplantation, homologous; unclassified drug; nonhuman; flow cytometry; protein function; t lymphocyte; t-lymphocytes; protein analysis; animal cell; mouse; animals; mice; steady state; animal experiment; animal model; transcription factor; mice, inbred balb c; mice, inbred c57bl; th2 cell; lymphocyte activation; lymphocyte culture test, mixed; hematologic malignancy; cd4+ t lymphocyte; kruppel-like transcription factors; graft versus host reaction; neoplasms, experimental; adoptive transfer; cytokine production; th1 cell; cell stimulation; bone marrow transplantation; graft vs host disease; chemokine receptor ccr7; graft versus leukemia effect; graft vs tumor effect; cell expansion; graft recipient; mixed lymphocyte reaction; natural killer t cell; alloimmunity; promyelocytic leukemia zinc finger; lymphocyte function associated antigen 1; lymphocyte transfer; cytokine response
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