Clinical applications - Graft engineering - T cell depletion - Applications


Allogeneic stem cell transplantation is a therapeutic option for the treatment of patients with distinct malignant and non-malignant diseases.32, 41
Active T cell depletion strategies can be used for haploidentical transplantation when an human leukocyte antigen (HLA) Id Sib or other HLA-matched related or unrelated donor is not available. CliniMACS technology enables the active depletion of B cells, T cells, or T cell subsets from the graft (CD3/CD19 depletion, TCRα/β/CD19 depletion). These depleted grafts have been used in the context of reduced intensity conditioning (RIC) regimens.24, 33, 34

CD3/CD19 depletion:
Clinical investigation during recent years has focused on treatment of hematological malignancies but, to a certain extent, solid tumor disease and non-malignant disease have also been the subject of clinical studies35, 36. Data have been acquired for patient populations, both children and adults, which demonstrate improved engraftment and immune reconstitution 33, 37-39. The authors conclude that CD3/CD19 depletion for graft engineering under RIC is a promising approach for patients without a matched related donor.
Especially children and elderly patients potentially benefit from the strategy of RIC.
Recent findings show that a CD3/CD19 depletion graft engineering strategy for non-HLA identical donor stem cell transplantation in children resulted in a remarkable cumulative TRM rate of only 10.7% - a result which was previously only found in HLA Id Sib transplantation40.

TCRα/β/CD19 depletion:
Results are accumulating on a most innovative active T cell depletion strategy which is based on TCRα/β/CD19 depletion of HLA-mismatched stem cell grafts for treatment of children with advanced malignant and non-malignant disease under RIC.29, 34 Patients showed a rapid and sustained engraftment, a rapid immune reconstitution, and a low incidence of graft-versus-host disease (GvHD). More recent data show that promising data could be generated not only on the basis of RIC but also after myeloablative conditioning, even when no post-transplant GvHD prophylaxis was administered 30.

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