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Introduction and non-technical Summary

The immune system is highly effective at removing large-numbers of virally infected cells without damaging normal non-infected cells, however it often remains oblivious and unresponsive to abnormal cancer cells. For the last four decades, cancer researchers working in the field of cancer immunotherapy have tried to trigger the immune system into recognizing and killing established cancers.

Recently, a form of immunotherapy known as adoptive immunotherapy (see cartoon, right), has demonstrated benefit to some cancer patients. With this form of immunotherapy, T-cells, a component of the immune system are first isolated from the patient's blood, and modified outside the body. After testing for effectiveness and purity, administered back to the patient.

T-cells are immune cells, which recognize and kill virally infected cells. In certain cancers e.g. melanoma, it is possible to select and expand cancer-specific T-cells in the laboratory and administer them back to the patient with resulting destruction of the cancer. This kind of treatment has been greatly limited since generating T-cells specific to cancer cells is difficult for most cancers. Recently, gene-therapy techniques allow us to “re-programme” T-cells by introducing a new T-cell receptor (TCR)(see cartoon). This has the potential to greatly widen the different cancers that can be targeted by T-cells.

T-cells often lack the correct T-cell receptor (TCR) to recognize targets (antigens) on tumour cells. T-cells in patients with cancer hence fail to recognize and kill cancer cells. We can remove some T-cells from a patient’s blood and modify them using gene-therapy methods by adding a tumour-specific receptor. Once administered back to the patient, these “re-programmed” T-cells should recognize and kill cancer cells.

T-cells often lack the correct T-cell receptor (TCR) to recognize targets (antigens) on tumour cells. T-cells in patients with cancer hence fail to recognize and kill cancer cells. We can remove some T-cells from a patient’s blood and modify them using gene-therapy methods by adding a tumour-specific receptor. Once administered back to the patient, these “re-programmed” T-cells will recognize and kill cancer cells.

Although this idea of TCR transfer seems simple, it requires use of complex molecular biology and gene-therapy techniques. It is only recently that the technology is sufficiently advanced and robust to allow us to consider a clinical study. The CHILDHOPE consortium will work to overcome scientific, technical and regulatory barriers to take this approach to clinical studies.

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Dr Eve-Marie NEIDHARDT-BERARD
Cellular Therapy, 28 rue Laennec - 69373 Lyon cedex 08 - France
assistant +33-478782843; office: +33-478785100; fax : +33-478782703