Autoimmune B-cell lymphopenia after successful adoptive therapy with telomerase-specific T lymphocytes
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- Stefano Ugel
- Department of Oncology and Surgical Sciences, Padova;
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- Elisa Scarselli
- Istituto di Ricerca di Biologia Molecolare (IRBM), Merck Sharp & Dohme Research Laboratories, Pomezia;
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- Manuela Iezzi
- Aging Research Center (CeSI), G. d'Annunzio University Foundation, Chieti Scalo;
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- Carmela Mennuni
- Istituto di Ricerca di Biologia Molecolare (IRBM), Merck Sharp & Dohme Research Laboratories, Pomezia;
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- Tania Pannellini
- Aging Research Center (CeSI), G. d'Annunzio University Foundation, Chieti Scalo;
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- Francesco Calvaruso
- Istituto di Ricerca di Biologia Molecolare (IRBM), Merck Sharp & Dohme Research Laboratories, Pomezia;
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- Barbara Cipriani
- Istituto di Ricerca di Biologia Molecolare (IRBM), Merck Sharp & Dohme Research Laboratories, Pomezia;
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- Raffaele De Palma
- Department of Clinical and Experimental Medicine, Second University of Naples, Centro Regionale di Competenza in Genomica per la Ricerca Applicata, Napoli;
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- Lucia Ricci-Vitiani
- Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome; and
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- Elisa Peranzoni
- Department of Oncology and Surgical Sciences, Padova;
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- Piero Musiani
- Aging Research Center (CeSI), G. d'Annunzio University Foundation, Chieti Scalo;
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- Paola Zanovello
- Department of Oncology and Surgical Sciences, Padova;
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- Vincenzo Bronte
- Istituto Oncologico Veneto (IOV), Padova, Italy
抄録
<jats:title>Abstract</jats:title> <jats:p>Telomerase reverse transcriptase (TERT) is a good candidate for cancer immunotherapy because it is overexpressed in 85% of all human tumors and implicated in maintenance of the transformed phenotype. TERT-based cancer vaccines have been shown to be safe, not inducing any immune-related pathology, but their impact on tumor progression is modest. Here we show that adoptive cell therapy with the use of high-avidity T lymphocytes reactive against telomerase can control the growth of different established tumors. Moreover, in transgenic adenocarcinoma mouse prostate mice, which develop prostate cancer, TERT-based adoptive cell therapy halted the progression to more aggressive and poorly differentiated tumors, significantly prolonging mouse survival. We also demonstrated that human tumors, including Burkitt lymphoma, and human cancer stem cells, are targeted in vivo by TERT-specific cytotoxic T lymphocytes. Effective therapy with T cells against telomerase, different from active vaccination, however, led to autoimmunity marked by a consistent, although transient, B-cell depletion in primary and secondary lymphoid organs, associated with alteration of the spleen cytoarchitecture. These results indicate B cells as an in vivo target of TERT-specific cytotoxic T lymphocytes during successful immunotherapy.</jats:p>
収録刊行物
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- Blood
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Blood 115 (7), 1374-1384, 2010-02-18
American Society of Hematology