Journal
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
Volume 20, Issue 5, Pages 705-716Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.bbmt.2014.01.032
Keywords
Naive T cells; Memory T cells; Graft-versus-host disease; Graft engineering; Selective T cell depletion; Immune reconstitution
Categories
Funding
- NIH [CA18029, CA 136551, CA15704, DK56465]
- NIH Rapid Access to Intervention Development (RAID) [298]
- Burroughs Wellcome Fund
- Damon Runyon Cancer Research Foundation [CI-57-11]
- National Cancer Institute [K23CA154532]
- Leukemia and Lymphoma Society
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Graft-versus-host disease (GVHD) is a frequent major complication of allogeneic hematopoietic cell transplantation (HCT). Approaches that selectively deplete T cells that cause GVHD from allogeneic stem cell grafts and preserve T cells specific for pathogens may improve HO' outcomes. It has been hypothesized that the majority of T cells that can cause GVHD reside within the naive T cell (T-N) subset, and previous studies performed in mouse models and with human cells in vitro support this hypothesis. As a prelude to translating these findings to the clinic, we developed and evaluated a novel 2-step clinically compliant procedure for manipulating peripheral blood stem cells (PBSC) to remove TN, preserve CD34(+) hematopoietic stem cells, and provide for a fixed dose of memory T cells (T-M) that includes T cells with specificity for common opportunistic pathogens encountered after HO'. Our studies demonstrate effective and reproducible performance of the immunomagnetic cell selection procedure for depleting TN. Moreover, after cell processing, the CD45RA-depleted PBSC products are enriched for CD4(+) and CD8(+) TM with a central memory phenotype and contain TM cells that are capable of proliferating and producing effector cytokines in response to opportunistic pathogens. (C) 2014 American Society for Blood and Marrow Transplantation.
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