Re-targeting T-cells against cancer by gene-transfer of tumor-reactive receptors

Abstract

Background: Adoptive transfer of T-lymphocytes is a promising treatment for a variety of malignancies, but is often not feasible due to difficulties in generating T-cells reactive with the targeted antigen from patients. To facilitate rapid generation of cells for therapy, T-cells can be programmed with genes encoding for an antigen-specific T-cell receptor (TCR) or chimeric receptors. Objective: To discuss the molecular design and selected pitfalls of TCR gene modified T-cells and T-cells expressing chimeric receptors, so called T-bodies. Methods: A selected review of the recent literature. Conclusion: Clinical trials report so far only limited efficacy of adoptively transferred genetically modified T-cells. However, the recent progress in engineering tumor-reactive T cells is providing a promising basis to further explore this treatment modality.

Keywords::

• clinical trial
• genetic engineering
• T-body
• TCR gene transfer

Acknowledgment

This work is support by the ZonMW (40-40300-98-07003). We are thankful to the helpful discussions with Z Eshhar, PD Greenberg and M Theobald.

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