Research Update
Turning T cells to the task of fighting cancer

CMAJ 2000;162:1604

"There are cells in the body that are specialized in the function of presenting antigens to T cells," says lead researcher Dr. Michel Sadelain. "These cells, termed 'antigen-presenting cells,' naturally express a cohort of molecules that render them effective in this task. However, the generation of such cells for the purpose of inducing specific T cells is labour-intensive and time-consuming. We therefore examined what are the minimal components needed to make genetically engineered cells that are potent activators of T cells that are able to recognize and destroy tumour cells."

Sadelain and his colleagues used mouse cells to stimulate the expansion of human tumour-reactive T cells in the laboratory. They found that introducing just 6 genes was enough to create a cell that efficiently stimulates and amplifies human cytotoxic T lymphocytes that break down melanoma cells in vitro. Three genes are used to generate the peptide complex that directly engages the T cell receptor. The other 3 genes enhance T cell activation by engaging other receptors expressed by the responding T cell.

"To our surprise, these artificial antigen-presenting cells worked at least as well as dendritic cells, the most potent naturally occurring antigen-presenting cells, under the experimental conditions used so far," says Dr. Sadelain.

The next step, he adds, is to confirm that artificial antigen-presenting cells can be generally applied to induce tumour-specific T cells in the laboratory. "We will initially focus on antigens found in lymphomas, leukemias and prostate cancer. We also plan to assess the efficacy of these T cells in animal studies. We intend to develop a system that could also permit stimulation of T cells against more than 1 antigen at a time." — Donalee Moulton, Halifax

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