T cells engineered with a T cell receptor against the prostate antigen TARP specifically kill HLA-A2+ prostate and breast cancer cells.
Proc Natl Acad Sci U S A
; 109(39): 15877-81, 2012 Sep 25.
Article
en En
| MEDLINE
| ID: mdl-23019373
ABSTRACT
To produce genetically engineered T cells directed against prostate and breast cancer cells, we have cloned the T-cell receptor recognizing the HLA-A2-restricted T-cell receptor γ-chain alternate reading-frame protein (TARP)(4-13) epitope. TARP is a protein exclusively expressed in normal prostate epithelium and in adenocarcinomas of the prostate and breast. Peripheral blood T cells transduced with a lentiviral vector encoding the TARP-TCR proliferated well when exposed to peptide-specific stimuli. These cells exerted peptide-specific IFN-γ production and cytotoxic activity. Importantly, HLA-A2(+) prostate and breast cancer cells expressing TARP were also killed, demonstrating that the TARP(4-13) epitope is a physiologically relevant target for T-cell therapy of prostate and breast cancer. In conclusion, we present the cloning of a T cell receptor (TCR) directed against a physiologically relevant HLA-A2 epitope of TARP. To our knowledge this report on engineering of T cells with a TCR directed against an antigen specifically expressed by prostate cells is unique.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Neoplasias de la Próstata
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Neoplasias de la Mama
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Proteínas Nucleares
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Linfocitos T
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Antígeno HLA-A2
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Ingeniería Celular
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Inmunidad Celular
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Antígenos de Neoplasias
Límite:
Female
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Humans
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Male
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Año:
2012
Tipo del documento:
Article
País de afiliación:
Suecia