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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

2010; Wiley; Volume: 51; Issue: 3 Linguagem: Inglês

10.1111/j.1537-2995.2010.02940.x

1537-2995

Anita Schmitt, Torsten Tonn, Dirk H. Busch, Götz Ulrich Grigoleit, Hermann Einsele, Marcus Odendahl, Lothar Germeroth, Mark Ringhoffer, Simone Ringhoffer, Markus Wiesneth, Jochen Greiner, Detlef Michel, Thomas Mertens, Markus Rojewski, Martin B. Marx, Stephanie von Harsdorf, Hartmut Döhner, Erhard Seifried, Donald Bunjes, Michael Schmitt,

Immune Cell Function and Interaction

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.