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Infusion of donor-derived CD8+ memory T cells for relapse following allogeneic hematopoietic cell transplantation.


ABSTRACT: Murine models showed that CD8+CD44hi memory T (TM) cells could eradicate malignant cells without inducing graft-versus-host disease (GVHD). We evaluated the feasibility and safety of infusing freshly isolated and purified donor-derived phenotypic CD8+ TM cells into adults with disease relapse after allogeneic hematopoietic cell transplantation (HCT). Phenotypic CD8 TM cells were isolated after unmobilized donor apheresis using a tandem immunomagnetic selection strategy of CD45RA depletion followed by CD8+ enrichment. Fifteen patients received CD8+ TM cells at escalating doses (1 × 106, 5 × 106, or 10 × 106 cells per kg). Thirteen received cytoreduction before CD8+ TM cell infusion, and 9 had active disease at the time of infusion. Mean yield and purity of the CD8+ TM infusion were 38.1% and 92.8%, respectively; >90% had CD8+ T effector memory phenotype, cytokine expression, and secretion profile. No adverse infusional events or dose-limiting toxicities occurred; GVHD developed in 1 patient (grade 2 liver). Ten patients (67%) maintained or achieved response (7 complete response, 1 partial response, 2 stable disease) for at least 3 months after infusion; 4 of the responders had active disease at the time of infusion. With a median follow-up from infusion of 328 days (range, 118-1328 days), median event-free survival and overall survival were 4.9 months (95% confidence interval [CI], 1-19.3 months) and 19.6 months (95% CI, 5.6 months to not reached), respectively. Collection and enrichment of phenotypic CD8+ TM cells is feasible, well tolerated, and associated with a low incidence of GVHD when administered as a manipulated infusion of donor lymphocytes in patients who have relapsed after HCT. This trial was registered at www.clinicaltrials.gov as #NCT01523223.

SUBMITTER: Muffly L 

PROVIDER: S-EPMC5873230 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Infusion of donor-derived CD8<sup>+</sup> memory T cells for relapse following allogeneic hematopoietic cell transplantation.

Muffly Lori L   Sheehan Kevin K   Armstrong Randall R   Jensen Kent K   Tate Keri K   Rezvani Andrew R AR   Miklos David D   Arai Sally S   Shizuru Judith J   Johnston Laura L   Meyer Everett E   Weng Wen-Kai WK   Laport Ginna G GG   Negrin Robert S RS   Strober Sam S   Lowsky Robert R  

Blood advances 20180301 6


Murine models showed that CD8<sup>+</sup>CD44<sup>hi</sup> memory T (T<sub>M</sub>) cells could eradicate malignant cells without inducing graft-versus-host disease (GVHD). We evaluated the feasibility and safety of infusing freshly isolated and purified donor-derived phenotypic CD8<sup>+</sup> T<sub>M</sub> cells into adults with disease relapse after allogeneic hematopoietic cell transplantation (HCT). Phenotypic CD8 T<sub>M</sub> cells were isolated after unmobilized donor apheresis using a t  ...[more]

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