Konference: 2007 49th ASH Annual Meeting - účast ČR
Kategorie: Maligní lymfomy a leukémie
Téma: Postery
Číslo abstraktu: 3250
Autoři: RNDr. Eva Matějková; RNDr. Ivana Burešová; Petra Vidláková; Drahomíra Kyjovská; Ellen S. Vitetta, Ph.D.; Prof. MUDr. Jaroslav Michálek, Ph.D.
(Intr. by A. John Barrett)
A major challenge in the field of hematopoietic stem cell transplantation (HSCT) is to prevent the alloreactivity of donor T-cells which leads to acute graft-versus-host disease (GVHD) while preserving a graft-versus-tumor (GVT) effect. Selective depletion using anti-CD25 immunotoxin (IT) can eliminate harmful alloreactive T-cells while preserving other donor T-cells with antileukemic/antitumor reactivity. We have used irradiated peripheral blood mononuclear cells (PBMC) from cancer patients and healthy donor PBMC as responder cells in primary mixed leukocyte reaction (MLR).To prepare GVL/GVT-specific T-cells, alloreactive T-cells in primary MLR were depleted with anti-CD25 IT. The remaining T-cells had insignificant alloreactivity in secondary MLR. Allodepleted donor cells were then repeatedly stimulated using purified leukemia/tumor cells from the same cancer patient. Leukemia/tumor-reactive donor T-cells were purified by immunomagnetic separation on the basis of INF-g production. 23 MLRs (12 with acute myeloid leukemia cells, 3 with acute lymphocytic leukemia cells and 8 with renal carcinoma cells) were performed. Selective depletion of alloreactive donor T-cells with anti-CD25 IT led to more than 2log depletion (99.2-100%, median 99.7%). Graft-versus-leukemia (GVL) effect of donor T-cells was well preserved (4.7% of donor T cells were GVL-reactive) while the graft-versus-host (GVH) reactivation of donor cells was negligible even after repeated stimulation with patients non-leukemic PBMC. In the case of renal cell carcinoma, GVT effect was less dominant (1.8% of donor T cells were GVT-reactive clones) and GVH reactivation appeared in 2.4% of donor T cells. In conclusion, it is possible to selectively deplete donor alloreactive T-cells with anti-CD25 IT. In case of patients with leukemia, a strong GVL reactivity was noticed in allodepleted donor T cells while in case of renal cell carcinoma the GVT effect was less dominant and associated with mild GVH-reactivation. Supported by the Ministry of Education of the Czech Republic, NPVII-2B06058.
A major challenge in the field of hematopoietic stem cell transplantation (HSCT) is to prevent the alloreactivity of donor T-cells which leads to acute graft-versus-host disease (GVHD) while preserving a graft-versus-tumor (GVT) effect. Selective depletion using anti-CD25 immunotoxin (IT) can eliminate harmful alloreactive T-cells while preserving other donor T-cells with antileukemic/antitumor reactivity. We have used irradiated peripheral blood mononuclear cells (PBMC) from cancer patients and healthy donor PBMC as responder cells in primary mixed leukocyte reaction (MLR).To prepare GVL/GVT-specific T-cells, alloreactive T-cells in primary MLR were depleted with anti-CD25 IT. The remaining T-cells had insignificant alloreactivity in secondary MLR. Allodepleted donor cells were then repeatedly stimulated using purified leukemia/tumor cells from the same cancer patient. Leukemia/tumor-reactive donor T-cells were purified by immunomagnetic separation on the basis of INF-g production. 23 MLRs (12 with acute myeloid leukemia cells, 3 with acute lymphocytic leukemia cells and 8 with renal carcinoma cells) were performed. Selective depletion of alloreactive donor T-cells with anti-CD25 IT led to more than 2log depletion (99.2-100%, median 99.7%). Graft-versus-leukemia (GVL) effect of donor T-cells was well preserved (4.7% of donor T cells were GVL-reactive) while the graft-versus-host (GVH) reactivation of donor cells was negligible even after repeated stimulation with patients non-leukemic PBMC. In the case of renal cell carcinoma, GVT effect was less dominant (1.8% of donor T cells were GVT-reactive clones) and GVH reactivation appeared in 2.4% of donor T cells. In conclusion, it is possible to selectively deplete donor alloreactive T-cells with anti-CD25 IT. In case of patients with leukemia, a strong GVL reactivity was noticed in allodepleted donor T cells while in case of renal cell carcinoma the GVT effect was less dominant and associated with mild GVH-reactivation. Supported by the Ministry of Education of the Czech Republic, NPVII-2B06058.
Abstract #3250 appears in Blood, Volume 110, issue 11, November 16, 2007
Keywords: Graft-versus-Host Disease (GVHD)|Graft-versus-Tumor
Effect|T Cell Depletion
Disclosure: No relevant conflicts of interest to declare.
Monday, December 10, 2007 5:00 PM
Session Info: Poster Session: Experimental Transplantation: GVHD
and GVL (5:00 p.m.-7:00 p.m.)
Datum přednesení příspěvku: 10. 12. 2007
