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


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.


CONCLUSIONS
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.
Department 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
Anita
A
Schmitt
Torsten
T
Tonn
Dirk H
DH
Busch
Götz Ulrich
GU
Grigoleit
Hermann
H
Einsele
Marcus
M
Odendahl
Lothar
L
Germeroth
Mark
M
Ringhoffer
Simone
S
Ringhoffer
Markus
M
Wiesneth
Jochen
J
Greiner
Detlef
D
Michel
Thomas
T
Mertens
Markus
M
Rojewski
Martin
M
Marx
Stephanie
S
von Harsdorf
Hartmut
H
Döhner
Erhard
E
Seifried
Donald
D
Bunjes
Michael
M
Schmitt
D019264:Adoptive Transfer; D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003587:Cytomegalovirus / Q000276:immunology*; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000276:immunology / Q000628:therapy; D036102:Peripheral Blood Stem Cell Transplantation; D010750:Phosphoproteins / Q000276:immunology; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology / Q000628:therapy; D014184:Transplantation, Homologous; D014763:Viral Matrix Proteins / Q000276:immunology
D010750:Phosphoproteins; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa