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ctt-journal > Odendahl et al. (Abstract)

Odendahl et al. (Abstract)

Cellular Therapy and Transplantation (CTT), Vol. 3, No. 12
doi: 10.3205/ctt-2011-No12-abstract78

© The Authors. This abstract is provided under the following license: Creative Commons Attribution 3.0 Unported

Abstract accepted for "5th Raisa Gorbacheva Memorial Meeting Hematopoietic Stem Cell Transplantation in Children and Adults", Saint Petersburg, Russia, September 18–20, 2011

Preliminary Program

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Treatment of recurrent CMV viremia after allogeneic stem cell transplantation using untouched CMV specific donor derived CD3+CD8+ T Lymphocytes isolated using the Streptamer technology

M. Odendahl1,2,  U. Grigoleit3, L. Germeroth4, M. Neuenhahn5, D.H. Busch5, H. Einsele3, T. Tonn1,2

1Institute for Transfusion Medicine and Immunohaematology, Red Cross Blood Donor Service East, Dresden, Germany; 2Center for Regenerative Therapies Dresden (CRTD), Medical Faculty Carl Gustav Carus, Technical University Dresden, Germany; 3Department of Internal Medicine II, Division of Haematology and Oncology, Allogeneic Stem Cell Transplant Centre, Julius Maximilians University Medical Centre, Würzburg, Germany; 4Stage Cell Therapeutics, Goettingen, Germany; 5Institute for Medical Microbiology, Immunology, and Hygiene, Technische Universität München, Munich, Germany

Correspondence: Prof. Dr. Torsten Tonn, Institute for Transfusion Medicine and Immunohaematology, Red Cross Blood Donor Service East, Dresden, Germany, E-Mail: ttonn@spam is badblutspende.de

Abstract

Reactivation of CMV following hematopoietic stem cell transplantation remains a major cause of morbidity despite improved antiviral drug therapies. Selective restoration of CMV immunity by CMV-specific adoptive T-cell transfer in these chemotherapy-refractory CMV infections is the only alternative approach which has been shown to be effective and non-toxic. Several groups have demonstrated that chemotherapy-resistant CMV infections can be successfully treated with the adoptive transfer of donor derived CMV-specific T-cells. In principle, two different strategies to obtain sufficient amounts of T-cells with defined specificity have been developed: in vitro expansion of T-cell lines or clones, or the direct ex vivo purification of epitope-specific T-cells by multimeric HLA complexes. In vitro expansion is time consuming, and leads to a loss of antiviral activity and limited persistence of transferred immunity. Binding of multimeric complexes can cause functional alterations of T-cells, and in addition, the cell preparation still contains the multimeric complexes used for isolation. Here the introduction of the MHC-I Streptamer technology based on reversible MHC-I multimer labelling, promises the isolation of “untouched” functionally unaltered virus-specific CD3+CD8+ T-cells readily available for adoptive immunotherapy. To prepare for a multicenter phase I/II study in patients with chemotherapy resistant recurrence of CMV viremia, our group has for the first time translated the MHC-I Streptamer technology into clinical scale. To date more than 15 clinical-scale isolations have been performed. Starting from an apheresis product with a mean frequency of 1.4% CMV-specific CD3+CD8+ T-cells among CD3+ T lymphocytes (ranging from 0.03 to 14.8%), the clinical scale immunomagnetic isolation process yielded a purity of up to 97.8% among T-cells, resulting in a cell dose of 6.1x107 (range 1.1x105–1.4x107) CMV-specific CD3+CD8+ T lymphocytes. After complete dissociation of Streptamer reagents, the isolated T-cells are transferred directly — without any in vitro expansion — to the respective CMV-infected patients. Initial results of the ongoing phase I/II clinical trial show that sufficient numbers of specific T-cells could be selected from all CMV sero-positive stem cell donors. In addition, we initiated extensive clonal analyses to demonstrate that the transferred T-cells participate in cellular immune responses against CMV after transfer. In conclusion, transfer of specific T-cells selected by Streptamers is a safe and feasible method to restore CMV-specific cellular immunity after allogeneic SCT. Moreover, the Streptamer technology may be readily expandable to other T-cell specificities, such as adenoviruses or leukemia-associated tumor antigens (e.g., WT-1).

Keywords: stem cell transplantation, CMV , cell therapy, donor lymphocyte infusion