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Expert Opin Biol Ther. 2010 May;10(5):749-62. doi: 10.1517/14712591003689998.

Enhanced T cell receptor gene therapy for cancer.

Author information

1
Max Delbrück Center for Molecular Medicine, Robert-Rössle-Strasse 10, D-13092 Berlin, Germany.

Abstract

IMPORTANCE OF THE FIELD:

Adoptive therapy with T cell receptor- (TCR-) redirected T cells has shown efficacy in mouse tumor models and first responses in cancer patients. One prerequisite to elicit effective anti-tumor reactivity is the transfer of high-avidity T cells. Their generation, however, faces several technical difficulties. Target antigens are often expressed at low levels and their recognition requires the use of high-affine receptors. Yet, mainly low-affinity TCRs have been isolated from tumor-infiltrating lymphocytes. Furthermore, upon transfer into a T cell the introduced receptor has to compete with the endogenous TCR.

AREAS COVERED IN THIS REVIEW:

This review discusses how the functional avidity of TCR-modified T cells can be enhanced by i) increasing the amount of introduced TCR heterodimers on the cell surface; and ii) generating receptors with high affinity. Risks of TCR gene therapy and possible safety mechanisms are discussed.

WHAT THE READER WILL GAIN:

The reader will gain an overview of the technical developments in TCR and T cell engineering.

TAKE HOME MESSAGE:

Despite technical obstacles, many advances have been made in the generation of high-avidity T cells expressing enhanced TCRs. Mouse studies and clinical trials will evaluate the effect of these improvements.

PMID:
20201709
DOI:
10.1517/14712591003689998
[Indexed for MEDLINE]

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