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Virus-specific T-cell banks for 'off the shelf' adoptive therapy of refractory infections

Bone Marrow Transplantation volume 51, pages 1163–1172 (2016)Cite this article

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Abstract

Adoptive immunotherapy with transplant donor-derived virus-specific T cells has emerged as a potentially curative approach for the treatment of drug-refractory EBV+lymphomas as well as CMV and adenovirus infections complicating allogeneic hematopoietic cell transplants. Adoptive transfer of HLA partially matched virus-specific T cells from healthy third party donors has also shown promise in the treatment of these conditions, with disease response rates of 50–76% and strikingly low incidences of toxicity or GVHD recorded in initial trials. In this review, we examine the reported experience with transplant donor and third party donor-derived virus-specific T cells, identifying characteristics of the viral pathogen, the T cells administered and the diseased host that contribute to treatment response or failure. We also describe the characteristics of virus-specific T-cell lines in our center’s bank and the frequency with which in vitro culture promotes expansion of immunodominant T cells specific for epitopes that are presented by a limited array of prevalent HLA alleles, which facilitates their broad applicability for treatment.

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Acknowledgements

We gratefully acknowledge the efforts of the Marrow Transplantation Services in Medicine and Pediatrics at Memorial Sloan Kettering Cancer Center and the National Marrow Donor Program in the support of these studies. Partial funding for this work was provided by National Institutes of Health grants NCI CA23766 NCI R21 CA162002 and P30 CA008748 and by the Major Family Fund for Cancer Research, and the Claire Tow Chair in Pediatric Oncology Research.

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  1. Department of Pediatrics, Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    R J O'Reilly, S Prockop, A N Hasan & E Doubrovina

  2. Department of Medicine, Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    R J O'Reilly & G Koehne

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Correspondence to R J O'Reilly.

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Following completion of studies conducted at MSKCC that are summarized in this review, Atara Biotherapeutics licensed the MSKCC banks of EBV and CMV-specific T-cell lines. As a result, Richard J O’Reilly, Aisha N Hasan, Ekaterina Doubrovina and Guenther Koehne have received royalties from Atara Biotherapeutics. Ekaterina Doubrovina has also received consulting fees from Atara Biotherapeutics.

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O'Reilly, R., Prockop, S., Hasan, A. et al. Virus-specific T-cell banks for 'off the shelf' adoptive therapy of refractory infections. Bone Marrow Transplant 51, 1163–1172 (2016). https://doi.org/10.1038/bmt.2016.17

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