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June 30, 2006

Using Gene therapy to rev up t-cells and stem cells against cancer

Gene therapy helps fight cancer by boosting the immune system. Ongoing and planned human tests take a promising approach to fighting cancer by boosting the immune system. Cancer cells hide in plain sight. The healthy immune system is precisely tuned to kill diseased cells, but it often falters when it comes to cancer cells. Researchers have tried many ways of bolstering the immune system’s response to cancer -- with limited success. But two new gene therapy approaches show promise.

One, now in human testing, uses gene therapy to help the immune system better recognize specific kinds of cancer cells. Another, already used to eradicate tumors in mice, uses gene therapy to alter stem cells, which in turn make immune cells that combat the specific cancer -- a treatment that would last a lifetime.

Baltimore and Rosenberg are both using gene therapy to mobilize T cells against cancer. First, they remove T cells from a patient who has recovered from, for example, a melanoma tumor. From these cells, they clone a gene whose protein product, a T cell receptor, has a strong affinity for a melanoma antigen. Then they construct a virus that can deliver this gene to other T cells.

Baltimore’s lab research has gone beyond T cells to the immune cells’ precursor, stem cells. Throughout life, stem cells in the bone marrow replenish blood cells, including those involved in the immune system like T cells. Because stem cells are continuously replenishing the immune system, giving them a gene that combats cancer would mean “a life-long supply of tumor-specific T cells,” says Baltimore. Using the stem cell technique in mice with existing tumors (while providing mice with supplements of another type of immune cell) leads mice to completely destroy their tumors, says Lili Yang, a research in Baltimore’s lab.

Baltimore won the Nobel prize in medicine in 1975 for his work on the kind of viruses used in gene therapy, and is now working on developing stem cell-targeted viruses.

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