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Transfusion. 2011 Mar;51(3):591-9. doi: 10.1111/j.1537-2995.2010.02940.x. Epub 2010 Dec 6.

Adoptive transfer and selective reconstitution of streptamer-selected cytomegalovirus-specific CD8+ T cells leads to virus clearance in patients after allogeneic peripheral blood stem cell transplantation.

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  • 1Department of Internal Medicine III, the Institute for Transfusion Medicine, and the Institute for Virology, University of Ulm, Ulm, Germany. michael.schmitt@med.uni-rostock.de

Abstract

BACKGROUND:

Cytomegalovirus (CMV) disease constitutes a serious complication after allogeneic stem cell transplantation. For the clearance of CMV, CD8+ T cells are pivotal.

STUDY DESIGN AND METHODS:

Here, the novel streptamer technology was used at good manufacturing practice (GMP) level for adoptive transfer of CMV-specific T cells into acute leukemia patients with recurrent high CMV antigenemia after allogeneic stem cell transplantation.

RESULTS:

After a single transfusion, the frequency of CMV-specific CD8+CD45RA+CCR7- effector T cells increased dramatically from 0.0% to a maximum of 27.1% of all T cells. These T cells were clearly donor derived and did not stem from intrinsic reconstitution, as demonstrated by analysis of 1) donor chimerism through single-tandem repeats, 2) T-cell receptor excision circles, and 3) Vβ-chain typing by polymerase chain reaction. Clinically, the specific T-cell transfer resulted in a persistent clearance of the CMV antigenemia, which allowed the patients to discontinue toxic antiviral drug therapy without further high-level reactivation of CMV, demonstrating the power of the streptamer technology.

CONCLUSION:

Taken together, the streptamer technology offers the advantage of selecting virus-specific CD8+ T cells at GMP level for adoptive T-cell transfer, thus inducing long-lasting specific CD8+ T-cell responses without increasing the risk for graft-versus-host disease.

© 2010 American Association of Blood Banks.

PMID:
21133926
[PubMed - indexed for MEDLINE]
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