Gene Therapy of Patient-Derived T Lymphocytes to Target and Eradicate Colorectal Hepatic Metastases.

Autor: Sheen, Aali J., Irlam, Joely, Kirillova, Natalia, Guest, Ryan D., Sherlock, David J., Hawkins, Robert E., Gilham, David E.
Zdroj: Diseases of the Colon & Rectum; Jun2003, Vol. 46 Issue 6, p793-804, 12p
Abstrakt: PURPOSE: The overall aim of this study was to develop a novel treatment for colorectal cancer based on the use of gene therapy. Genetic modification of T lymphocytes has been used to specifically target and kill tumor cell lines directly. To test the efficacy of this method with clinically relevant materials, this study investigated the potential of T lymphocytes derived from patients with advanced colorectal disease to target autologous primary tumor material. METHODS: T lymphocytes isolated preoperatively were modified genetically with recombinant retroviruses encoding CD3ζ-based chimeric immune receptors and were tested for functional activity against freshly isolated autologous tumor cells harvested from hepatic colorectal metastases. RESULTS: Patient-derived T cells were successfully transduced, and chimeric immune receptor expression was confirmed. Carcinoembryonic antigen expression on freshly isolated colorectal tumor cells was also demonstrated by molecular and immunohistochemical techniques. T cells expressing the anticarcinoembryonic antigen receptor were specifically activated by coculture with disaggregated or intact, diced tumor, whereas control non-carcinoembryonic antigen-targeted T-cell populations failed to activate. CONCLUSIONS: These results indicate that gene-targeted primary T lymphocytes depict specific functional activity against autologous colorectal tumor cells. This evidence indicates that chimeric immune receptor-expressing T cells may be able to circumvent the mechanisms used by tumor cells to avoid immune cell activity in vivo. This study emphasizes the potential of this approach as a therapy for carcinoembryonic antigen-expressing primary colorectal tumor and its metastases. [ABSTRACT FROM AUTHOR]
Databáze: Supplemental Index
Externí odkaz: