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

Lori Muffly, Kevin Sheehan, Randall Armstrong, Kent Jensen, Keri Tate, Andrew R. Rezvani, David Miklos, Sally Arai, Judith Shizuru, Laura Johnston, Everett Meyer, Wen Kai Weng, Ginna G. Laport, Robert S. Negrin, Sam Strober, Robert Lowsky

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)681-690
Number of pages10
JournalBlood Advances
Volume2
Issue number6
DOIs
StatePublished - Mar 27 2018
Externally publishedYes

ASJC Scopus subject areas

  • Hematology

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