Abstract
The ability to selectively deplete or enrich cells of specific phenotype by immunomagnetic selection to reduce the risk of GVHD holds significant promise for application in adoptive immunotherapy. Current clinical-scale approaches for T-cell depletion (e.g., CD34(+) selection, CD3(+) depletion), usually deplete gammadelta T cells, which may be advantageous in mediating graft-versus-tumor (GVT) effects and augmenting the innate immune response against infections. Here, we present a new method for depletion of T cells with potential GVHD reactivity by using a single-step immunomagnetic protocol, which efficiently depletes CD4(+) and CD8(+) alphabeta T cells under good manufacturing practice (GMP) conditions. Depletion from unstimulated leukapheresis products (n=6) containing up to 2.0 x 10(10) cells showed high efficiency (mean log depletion of CD4(+) cells: 4.12, CD8(+) cells: 3.77). In addition, immunomagnetic CD4/CD8 depletion resulted in passive enrichment of innate lymphocytes (mean recovery of natural killer (NK) cells: 38%, gammadelta T cells: 50%). We demonstrated that gammadelta/NK cells preserved their proliferative and cytotoxic capacity and conclude that simultaneous large-scale depletion of CD4(+)/CD8(+) T cells is feasible and can be performed under GMP conditions with high-depletion efficacy for alphabeta T cells and recovery of functionally intact innate effector lymphocytes for potential use in adoptive immunotherapy studies.
Highlights
Allogeneic hematopoietic stem cell transplantation (HSCT) has been shown to provide a potential curative option for a variety of hematological and nonhematological diseases.the use of HSCT is limited by the availability of a suitable matched related or unrelated donor and significant transplant-associated complications such as GVHD, infections and conditioning regimen-related toxicities
Immunomagnetic CD4/CD8 depletion resulted in passive enrichment of innate lymphocytes (mean recovery of natural killer (NK) cells: 38%, cd T cells: 50%)
We demonstrated that cd/NK cells preserved their proliferative and cytotoxic capacity and conclude that simultaneous large-scale depletion of CD4 þ /CD8 þ T cells is feasible and can be performed under good manufacturing practice (GMP) conditions with high-depletion efficacy for ab T cells and recovery of functionally intact innate effector lymphocytes for potential use in adoptive immunotherapy studies
Summary
Clinical-scale single-step CD4 þ and CD8 þ cell depletion for donor innate lymphocyte infusion (DILI). We present a new method for depletion of T cells with potential GVHD reactivity by using a single-step immunomagnetic protocol, which efficiently depletes CD4 þ and CD8 þ ab T cells under good manufacturing practice (GMP) conditions. Immunomagnetic CD4/CD8 depletion resulted in passive enrichment of innate lymphocytes (mean recovery of natural killer (NK) cells: 38%, cd T cells: 50%). We demonstrated that cd/NK cells preserved their proliferative and cytotoxic capacity and conclude that simultaneous large-scale depletion of CD4 þ /CD8 þ T cells is feasible and can be performed under GMP conditions with high-depletion efficacy for ab T cells and recovery of functionally intact innate effector lymphocytes for potential use in adoptive immunotherapy studies. Bone Marrow Transplantation (2008) 41, 643–650; doi:10.1038/sj.bmt.1705942; published online 26 November 2007 Keywords: gd T cells; NK cells; CD4/CD8 depletion; adoptive immunotherapy
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