This study was presented at the American Hepato-Pancreato-Biliary Association 11th Annual Meeting, Miami, FL, USA.
Engineered T cells for pancreatic cancer treatment
Article first published online: 20 JUL 2011
© 2011 International Hepato-Pancreato-Biliary Association
Volume 13, Issue 9, pages 643–650, September 2011
How to Cite
Katari, U. L., Keirnan, J. M., Worth, A. C., Hodges, S. E., Leen, A. M., Fisher, W. E. and Vera, J. F. (2011), Engineered T cells for pancreatic cancer treatment. HPB, 13: 643–650. doi: 10.1111/j.1477-2574.2011.00344.x
- Issue published online: 15 AUG 2011
- Article first published online: 20 JUL 2011
- Received 10 March 2011; accepted 24 May 2011
- chimeric antigen receptor;
- pancreatic cancer;
- prostate stem cell antigen
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 (Cr51) 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.