Autoimmune B-cell lymphopenia after successful adoptive therapy with telomerase-specific T lymphocytes

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, bu...

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Veröffentlicht in:Blood 2010-02, Vol.115 (7), p.1374-1384
Hauptverfasser: Ugel, Stefano, Scarselli, Elisa, Iezzi, Manuela, Mennuni, Carmela, Pannellini, Tania, Calvaruso, Francesco, Cipriani, Barbara, De Palma, Raffaele, Ricci-Vitiani, Lucia, Peranzoni, Elisa, Musiani, Piero, Zanovello, Paola, Bronte, Vincenzo
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container_end_page 1384
container_issue 7
container_start_page 1374
container_title Blood
container_volume 115
creator Ugel, Stefano
Scarselli, Elisa
Iezzi, Manuela
Mennuni, Carmela
Pannellini, Tania
Calvaruso, Francesco
Cipriani, Barbara
De Palma, Raffaele
Ricci-Vitiani, Lucia
Peranzoni, Elisa
Musiani, Piero
Zanovello, Paola
Bronte, Vincenzo
description 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.
doi_str_mv 10.1182/blood-2009-07-233270
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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. 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subjects Adenocarcinoma - immunology
Adenocarcinoma - therapy
Adoptive Transfer - methods
Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy
Animals
Applied cell therapy and gene therapy
B-Lymphocytes - immunology
B-Lymphocytes - pathology
Biological and medical sciences
Bone Marrow Cells - pathology
Cancer Vaccines
Cell Line, Tumor
Colonic Neoplasms
Disease Models, Animal
Hematologic and hematopoietic diseases
HLA-A2 Antigen - genetics
HLA-A2 Antigen - immunology
Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis
Lung Neoplasms
Lymphopenia - pathology
Male
Medical sciences
Melanoma
Mice
Mice, Inbred C57BL
Mice, Transgenic
Neoplasm Transplantation
Prostatic Neoplasms - immunology
Prostatic Neoplasms - therapy
Skin Neoplasms
Spleen - pathology
T-Lymphocytes - immunology
T-Lymphocytes - transplantation
Telomerase - immunology
Transfusions. Complications. Transfusion reactions. Cell and gene therapy
title Autoimmune B-cell lymphopenia after successful adoptive therapy with telomerase-specific T lymphocytes
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