Infusion of CD3/CD28 costimulated umbilical cord blood T cells at the time of single umbilical cord blood transplantation may enhance engraftment.

Autor: Hexner EO; Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania., Luger SM; Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania., Reshef R; Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania., Jeschke GR; Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania., Mangan JK; Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania., Frey NV; Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania., Frank DM; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania., Richman LP; Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania., Vonderheide RH; Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.; Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania., Aqui NA; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania., Rosenbach M; Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania., Zhang Y; Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, Pennsylvania., Chew A; Center for Cellular Immunotherapy, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania., Loren AW; Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania., Stadtmauer EA; Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania., Levine BL; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.; Center for Cellular Immunotherapy, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania., June CH; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.; Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.; Center for Cellular Immunotherapy, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania., Emerson SG; Columbia College of Physicians and Surgeons, Herbert Irving Comprehensive Cancer Center, New York., Porter DL; Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Jazyk: angličtina
Zdroj: American journal of hematology [Am J Hematol] 2016 May; Vol. 91 (5), pp. 453-60. Date of Electronic Publication: 2016 Apr 04.
DOI: 10.1002/ajh.24303
Abstrakt: Limited cell numbers in umbilical cord blood (UCB) grafts present a major impediment to favorable outcomes in adult transplantation, largely related to delayed or failed engraftment. The advent of UCB transplantation (UCBT) using two grafts successfully circumvents this obstacle, despite the engraftment of only one unit. Preclinical models suggested that the addition of UCB T cells at the time of transplant can enhance engraftment. We tested whether ex vivo activation by CD3/CD28 costimulation and expansion of T cells from a single UCB graft would be safe and feasible in adults with advanced hematologic malignancies, with an overall objective of optimizing engraftment in single unit UCBT. In this phase 1 study, recipients of single UCB units were eligible if the unit was stored in two adequate fractions. Dose limiting toxicity was defined as grade 3 or grade 4 GVHD within 90 days of UCBT. Four patients underwent UCBT; all were treated at the first dose level (10(5) cells/kg). At the 10(5) cells/kg dose level two subjects experienced grade 3 intestinal GVHD, thus meeting stopping criteria. For three subjects, neutrophil engraftment was early (12, 17, and 20 days), while one subject experienced primary graft failure. We observed early donor T cell trafficking and found that expanded T cells produced supraphysiologic levels of cytokines relevant to engraftment and to lymphoid differentiation and function. Taken together, these preliminary data suggest rapid engraftment in recipients of a single UCBT combined with relatively low doses of activated T cells, though potentially complicated by severe GVHD.
(© 2016 Wiley Periodicals, Inc.)
Databáze: MEDLINE
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