T lymphocytes isolated from patients with advanced colorectal cancer are suitable for gene immunotherapy approaches.
AffiliationCancer Research UK Department of Medical Oncology, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, University of Manchester, UK.
MetadataShow full item record
AbstractDespite improvements in treatment, the 5-year survival for metastatic colorectal cancer remains poor. Novel approaches such as gene immunotherapy are being investigated to improve treatment. Retroviral gene transfer methods have been shown to transduce primary human T lymphocytes effectively resulting in the expression of therapeutic genes. However, a number of defects have been identified in T lymphocytes isolated from patients bearing tumour, which may have critical implications for the development of gene-targeted T cells as an anticancer therapy. To address this issue, primary T lymphocytes were isolated from patients with advanced colorectal cancer and tested for their ability to be transduced and to express subsequently a chimeric immune receptor consisting of a single-chain antibody fragment antigen-binding moiety specific for carcinoembryonic antigen (CEA) fused to the T cell receptor (TCR) CD3zeta chain. In 10 out of 10 patients, T lymphocytes were transduced, expanded in the absence of selection and tested for functional activity against CEA-expressing tumour cells. In each case, functional-specific cytotoxic activity was observed. Negligible activity was found in control cultures. This study highlights the feasibility of patient-derived T lymphocytes as a source of immune cells for autologous gene immunotherapy approaches.
CitationT lymphocytes isolated from patients with advanced colorectal cancer are suitable for gene immunotherapy approaches. 2003, 88 (7):1119-27 Br. J. Cancer
JournalBritish Journal of Cancer
- A recombinant anti-carcinoembryonic antigen immunoreceptor with combined CD3zeta-CD28 signalling targets T cells from colorectal cancer patients against their tumour cells.
- Authors: Hombach A, Schlimper C, Sievers E, Frank S, Schild HH, Sauerbruch T, Schmidt-Wolf IG, Abken H
- Issue date: 2006 Aug
- Gene therapy of patient-derived T lymphocytes to target and eradicate colorectal hepatic metastases.
- Authors: Sheen AJ, Irlam J, Kirillova N, Guest RD, Sherlock DJ, Hawkins RE, Gilham DE
- Issue date: 2003 Jun
- Antitumor activity of chimeric immunoreceptor gene-modified Tc1 and Th1 cells against autologous carcinoembryonic antigen-expressing colon cancer cells.
- Authors: Sasaki T, Ikeda H, Sato M, Ohkuri T, Abe H, Kuroki M, Onodera M, Miyamoto M, Kondo S, Nishimura T
- Issue date: 2006 Sep
- Bypassing immunization: optimized design of "designer T cells" against carcinoembryonic antigen (CEA)-expressing tumors, and lack of suppression by soluble CEA.
- Authors: Nolan KF, Yun CO, Akamatsu Y, Murphy JC, Leung SO, Beecham EJ, Junghans RP
- Issue date: 1999 Dec
- Primary polyclonal human T lymphocytes targeted to carcino-embryonic antigens and neural cell adhesion molecule tumor antigens by CD3zeta-based chimeric immune receptors.
- Authors: Gilham DE, O'Neil A, Hughes C, Guest RD, Kirillova N, Lehane M, Hawkins RE
- Issue date: 2002 Mar-Apr