Selektivní deplece aloreaktivních T-lymfocytů a studium protinádorové aktivity specifických klonů T-lymfocytů u pacientů s leukémií
| Title in English | SELECTIVE DEPLETION OF ALLOREACTIVE T CELLS AND STUDY OF ANTI-TUMOR ACTIVITY OF SPECIFIC T CELL CLONES IN PATIENTS WITH LEUKEMIA |
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| Authors | |
| Year of publication | 2008 |
| Type | Article in Periodical |
| Magazine / Source | Klinická onkologie |
| MU Faculty or unit | |
| Citation | |
| Web | http://www.linkos.cz/vzdelavani/3_08/05.pdf |
| Field | Oncology and hematology |
| Keywords | lymphocyte depletion;graft-versus-host disease;immunotherapy;hematopoietic stem cell transplantation |
| Description | Background: Graft-versus-host disease (GVHD) is a severe complication of allogeneic transplantation of hematopoietic stem cells. Donor T cells play a major role in GVHD leading to the host tissue damage mainly the skin liver and gastrointestinal tract. A selective depletion using an anti-CD25 immunotoxin can eliminate harmful alloreactive T cells while preserving other donor T cells with antileukemic and antiinfectious reactivity. Patients and Methods: We performed 15 mixed lymphocyte reactions with clinical specimens from 12 patients with various types of leukemia (7x AML 3x ALL 1x CML 1x CLL) and PBMC from 15 healthy volunteers from Transfusive station FN Brno Bohunice. Results: In our experiments we have demonstrated, that antileukemic (GVL) effect of donor, especially CD4+ T cells was well preserved (7.46%), while unfavourable alloreactive (GVH) reaction of donor T cells was completely removed. The graft-versus-host (GVH) reactivation of donor cells was negligible ever after repeated stimulation with irradiated patients PBMC. Conclusion: We have shown that anti-CD25 immunotoxin (IT) RFT5-SMPT-dgA, launched against alfa chain for human interleukin 2 (IL-2)led to long-term selective depletion of alloreactive donor T cell clones while their antileukemic activity was well preserved. Base on our results the clinical phase I/II study was designed. This study was initiated in year 2007 in three clinical centers in Czech Republic. |
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