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Autoimmune B-cell lymphopenia after successful adoptive therapy with telomerase-specific T lymphocytes.
- Source :
-
Blood [Blood] 2010 Feb 18; Vol. 115 (7), pp. 1374-84. Date of Electronic Publication: 2009 Nov 10. - Publication Year :
- 2010
-
Abstract
- 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.
- Subjects :
- Adenocarcinoma immunology
Animals
B-Lymphocytes immunology
B-Lymphocytes pathology
Bone Marrow Cells pathology
Cancer Vaccines
Cell Line, Tumor
Colonic Neoplasms
Disease Models, Animal
HLA-A2 Antigen genetics
HLA-A2 Antigen immunology
Lung Neoplasms
Male
Melanoma
Mice
Mice, Inbred C57BL
Mice, Transgenic
Neoplasm Transplantation
Prostatic Neoplasms immunology
Skin Neoplasms
Spleen pathology
T-Lymphocytes immunology
Adenocarcinoma therapy
Adoptive Transfer methods
Lymphopenia pathology
Prostatic Neoplasms therapy
T-Lymphocytes transplantation
Telomerase immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1528-0020
- Volume :
- 115
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 19903903
- Full Text :
- https://doi.org/10.1182/blood-2009-07-233270