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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 and Yang have started a research group to translate their mouse success into a human therapy. Like Rosenberg, they will perform their first clinical trial with patients with advanced melanoma, and will work first with T cells rather than stem cells. “We have to do T cells first to look at the safety and efficacy profile, and [more work in] animal models is needed to find out what the requirements are” before moving to stem cell therapies, says James Economou, chief of surgical oncology at the University of California at Los Angeles Medical School. (Other institutions involved in the planned clinical trials include Children’s Hospital Los Angeles and the University of Southern California.) Baltimore hopes the group will treat its first patient next year.

The group will address safety concerns by delivering a single gene called TK along with the receptor gene. The added gene will make the T cells visible on PET scans; the group will work on imaging the therapy with the inventor of PET, Michael Phelps, professor molecular and medical pharmacology at UCLA. The TK gene can also act as a suicide gene: if patients’ T cells turn cancerous, the researchers will give them a drug toxic to cells making TK.

Baltimore has high hopes for his gene therapy work. Rather than having patients undergo the painful process of a bone marrow transplant, which is necessary to remove and replace the stem cells, “the holy grail is just to put the virus in humans and have it home to the stem cells.” 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.

If the current and planned clinical trials are a success, it would have a tremendous impact on cancer patients. “Although we can cure half of the people with cancer, half will die. That’s almost 600,000 deaths per year in the U.S.,” says Rosenberg. “So we’re looking for new treatments.”

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