Clinical applications - Graft engineering - T cell depletion - Background

Background

Active T cell depletion allows a focused depletion of unwanted cells from the graft while several populations of potential therapeutic benefit are preserved within the graft.

Active T and B cell depletion

CD3/CD19 depletion
In contrast to the strategy of CD34+ cell enrichment, active T and B cell depletion results in a graft that contains CD34+ stem cells, CD34 stem cells, other progenitor cells and natural killer (NK) cells, monocytes, and dendritic cells, which might have engraftment facilitating effects32. This active T cell depletion strategy is currently being evaluated, especially in combination with reduced intensity conditioning.12, 23, 24

TCRα/β depletion
Another possibility for active T cell depletion is provided by the CliniMACS® TCRα/β System.
Cells which are responsible for the development of graft-versus-host disease (GvHD) are thought to derive from the pool of TCRα/β+ T cells, whereas TCRγ/δ+ T cells and NK cells may bear graft-versus-leukemia (GvL) effects, engraftment facilitating functions, and may help to fight infections. 25-28
Thus, depletion of TCRα/β+ T cells may be a helpful tool to prevent GvHD, while preserving different cell populations of potential therapeutic value within the cellular product.29
The CliniMACS TCRα/β product line can also be used in combination with the CliniMACS CD19 Reagent to additionally remove the CD19+ B cells from the graft. 30

CD45RA depletion

CD45RA is expressed on naive T cells whereas memory T cells are CD45RA. CD45RA depletion results in a cellular product passively enriched for memory T cells, while naive T cells, which have the potential to induce GvHD, are depleted.31 The potential benefit of memory T cell infusion probably results from the high anti-infection potential of this cell type. It should be noted that CD45RA is also present on part of other lymphocytes and hematopoietic stem cells. This should be considered if memory T cell infusion is planned to be combined with the initial transplant. In exceptional cases it may happen that donors have CD45+ memory T cells. This should be tested prior to any clinical application.

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Miltenyi Biotec Inc.
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macs@miltenyibiotec.com
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