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.
The immune system is a complex network of many kinds of cells, some killers, some regulators. Researchers have tried intervening in several different places in this network to rally it against cancer. But “nobody has figured out a way to make cancer vaccines work,” says Steven Rosenberg, head of tumor immunology in the National Cancer Institute’s Center for Cancer Research.
Rosenberg’s group and another in southern California are trying a new approach by going after one of the most important cells in the immune system, the T cell. T cells have receptors that can recognize specific antigens – protein markers that can signal disease or infection – on other cells. Cancer cells bear antigens, but somehow, they shut down T cells’ activity. Cancer patients have T cells specific to their disease. These “look like perfectly good T cells but they don’t respond to cancer. We’re not sure how it happens,” says David Baltimore, president of the California Institute of Technology, who heads the California group.
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.
Rosenberg is currently conducting a clinical trial using a T cell receptor gene for melanoma in patients with advanced disease. Patients’ blood is drawn, their T cells are removed, incubated with the virus, then replaced. Rosenberg declined to discuss his results because it would jeopardize upcoming publication in a scientific journal. But he hopes to start clinical trials on other cancers soon: his group has isolated the receptor for an antigen made in large quantities in half of all common cancers, including those of the breast, lung, and prostate.