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• W2016075783 abstract "Separation of graft-vs.-leukemia effect (GVL) from graft-vs.-host disease (GVHD) is the phenomenon that patients with leukemia/lymphoma achieve complete remission without GVHD after allogeneic stem cell transplantation. We demonstrate in this study that separation of GVL from GVHD could be achieved using only unmanipulated mature T cells in a mouse model. Graded numbers (103–106) of purified T cells from C57BL/6 mice were transplanted into lethally irradiated BALB/c mice along with 1 × 107 T cell depleted bone marrow cells and 1 × 105 purified BCL1 cells (a BALB/c-origin leukemia/lymphoma cell line). As a negative control, T cell depleted bone marrow alone rescued all lethally irradiated recipients and all survived more than 100 days after transplantation without GVHD. All the recipients of T cell depleted bone marrow and BCL1 cells developed tumor and died within 21 days post transplantation. Addition of 1 × 103 T cells in the graft protected one out of five animals from developing tumor. Addition of 1 × 104 T cells protected all recipients from developing tumor and all survived more than 100 days after transplantation without GVHD. Addition of both 1 × 105 and 1 × 106 protected all animals from developing tumor. However, all animals in these two groups developed GVHD and the majority died before 50 days post transplantation. These data directly demonstrate that unmanipulated T cells alone can mediate GVL effect without causing GVHD in a given animal model using a carefully titrated dose. Based on these data, one can envision that separation of GVL from GVHD may be achievable in a selected model by any approach that is able to inhibit T cell function to a certain degree, specifically or non-specifically. Knowledge of this information is important in all animal models testing different approaches for the prevention of GVHD without loss of GVL. Unfortunately, separation of GVL from GVHD is very difficult to achieve in humans by using unmanipulated T cells alone due to unknown minimum dose required for induction of GVHD in individual patients. Therefore, in order to translate the findings into human setting, it will be important to determine not only whether separation of GVL from GVHD is achievable but also how wide the therapeutic window is. The therapeutic window will help to determine whether the approach is translatable in humans or not. Tabled 1Mature T Cells Alone Separate GVL From GVHDPresence of TumorBody Weight (gram)100-day SurvivalDay + 21Day + 98TCD BM alone—18.6 ± 0.919.1 ± 2.15/5TCDBM+ BCL15/514.7 ± 0.8*P < 0.05, compared with TCD BM alone.—0/5 1 × 1034/516.7 ± 2.1*P < 0.05, compared with TCD BM alone.15.0 ± 0.01/5 1 × 1040/518.5 ± 1.1*P < 0.05, compared with TCD BM alone.18.7 ± 2.05/5 1 × 1050/515.7 ± 1.6*P < 0.05, compared with TCD BM alone.14.7 ± 3.2*P < 0.05, compared with TCD BM alone.2/5 1 × 1060/514.9 ± 0.9*P < 0.05, compared with TCD BM alone.—0/5* P < 0.05, compared with TCD BM alone. Open table in a new tab" @default.
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• W2016075783 date "2005-02-01" @default.
• W2016075783 modified "2023-09-26" @default.
• W2016075783 title "Mature T cells alone separate GVL from GVHD: The need for better controls" @default.
• W2016075783 doi "https://doi.org/10.1016/j.bbmt.2004.12.143" @default.
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