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J Infect Dis. 2017 Nov 15;216(8):945-956. doi: 10.1093/infdis/jix357.

Cytomegalovirus-Specific T-Cell Transfer for Refractory Cytomegalovirus Infection After Haploidentical Stem Cell Transplantation: The Quantitative and Qualitative Immune Recovery for Cytomegalovirus.

Author information

1
Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation.
2
Beijing Engineering Lab for Cell Therapy, Beijing, China.
3
Peking-Tsinghua Center for Life Sciences.

Abstract

Background:

The efficiency and mechanisms of adoptive transfer of cytomegalovirus (CMV)specific T cells for refractory CMV infection after haploidentical stem cell transplantation (haplo-SCT) remain largely unknown.

Methods:

Thirty-two patients with refractory CMV infection who accepted treatment with adoptive CMV-specific T-cell infusion following haplo-SCT were prospectively enrolled. Another 32 patients with nonrefractory CMV infection after haplo-SCT were selected as control subjects. The phenotypical and functional characteristics of CMV-specific T cells were analyzed before and after cellular therapy in the refractory cohort, as well as in the nonrefractory cohort.

Results:

In the refractory cohort, 27 of the 32 treated patients exhibited CMV clearance within 4 weeks after adoptive T-cell transfer without recurrence. The in vivo expansion of CMV-specific T cells and improvements in the cytokine production and proliferation ability of the CMV-specific T cells were observed after cellular therapy. Moreover, a reduced expression of programmed death-1 (PD-1) on CMV-specific T cells was observed. However, in the remaining 5 patients who showed CMV recurrence 4 weeks after transfer, neither the quantity nor the function of CMV-specific T cells was restored.

Conclusions:

The adoptive transfer of CMV-specific T cells promotes quantitative and functional recovery of CMV-specific T cells to guard against refractory CMV infection after haplo-SCT.

KEYWORDS:

antiviral immunity; cytomegalovirus-specific T cells; haploidentical stem cell transplantation; refractory cytomegalovirus infection

PMID:
29029297
DOI:
10.1093/infdis/jix357
[Indexed for MEDLINE]

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