Engineered T cells for pancreatic cancer treatment.
HPB (Oxford)
; 13(9): 643-50, 2011 Sep.
Article
em En
| MEDLINE
| ID: mdl-21843265
ABSTRACT
OBJECTIVE:
Conventional chemotherapy and radiotherapy produce marginal survival benefits in pancreatic cancer, underscoring the need for novel therapies. The aim of this study is to develop an adoptive T cell transfer approach to target tumours expressing prostate stem cell antigen (PSCA), a tumour-associated antigen that is frequently expressed by pancreatic cancer cells.METHODS:
Expression of PSCA on cell lines and primary tumour samples was confirmed by immunohistochemistry. Healthy donor- and patient-derived T cells were isolated, activated in vitro using CD3/CD28, and transduced with a retroviral vector encoding a chimeric antigen receptor (CAR) targeting PSCA. The ability of these cells to kill tumour cells was analysed by chromium-51 (Cr(51)) release.RESULTS:
Prostate stem cell antigen was expressed on >70% of the primary tumour samples screened. Activated, CAR-modified T cells could be readily generated in clinically relevant numbers and were specifically able to kill PSCA-expressing pancreatic cancer cell lines with no non-specific killing of PSCA-negative target cells, thus indicating the potential efficacy and safety of this approach.CONCLUSIONS:
Prostate stem cell antigen is frequently expressed on pancreatic cancer cells and can be targeted for immune-mediated destruction using CAR-modified, adoptively transferred T cells. The safety and efficacy of this approach indicate that it deserves further study and may represent a promising novel treatment for patients with pancreatic cancer.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Pancreáticas
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Receptores de Antígenos de Linfócitos T
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Linfócitos T
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Terapia Genética
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Imunoterapia Adotiva
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Carcinoma Ductal Pancreático
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Anticorpos de Cadeia Única
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Antígenos de Neoplasias
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Proteínas de Neoplasias
Limite:
Humans
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article