Cancer results from cells gone wild. Proliferating out of control, the cells spawn malignant growths that can travel throughout the human body, spreading the disease. Some patients' immune systems are able to recognize such tumors and begin to attack them, and research has shown that boosting the patients' levels of such tumor-infiltrating lymphocytes can help defeat deadly cancer. Now scientists have transformed immune cells into cancer fighters outside the body--and prompted complete remission in two subjects when those cells were reintroduced.
Immune cells such as lymphocytes, also known as T cells and pictured in blue above, recognize health threats via special receptors on the cell surface. Steven Rosenberg of the National Cancer Institute and his colleagues first cloned the genes governing the cancer-recognizing receptor in immune cells from a patient who had successfully beaten back melanoma. The researchers introduced this genetic information into regular T cells from 17 melanoma patients via retrovirus.
After chemotherapy, these patients had severely weakened immune systems, with few actively circulating lymphocytes. The scientists infused the engineered lymphocytes back into their weakened systems and discovered that such cells could persist, making up between 9 percent and 56 percent of the T cell population one month after treatment in 15 of the 17 patients.
Two patients out of the 17 experienced profound benefits from this infusion. The engineered lymphocytes of a 52-year-old man with melanoma destroyed a tumor in his armpit and shrank a liver growth by 89 percent, allowing it to be removed. And the cancer-fighting T cells of a 30-year-old man dissipated a mass in his lung. Both remain disease-free 18 months after treatment and continue to exhibit high levels of the engineered immune cells in their blood. The study "represents the first time that gene manipulations have been shown to cause tumor regression in humans," Rosenberg notes. "We can take normal lymphocytes from patients and convert them to tumor-reactive cells."
The work--published online today by Science--shows considerable promise for cancers other than melanoma as well, including breast and lung cancers. Rosenberg and his team will now work to determine what sustains such engineered populations over the long-term. They will also explore whether treatments that showed benefits in mice when paired with the engineered lymphocytes will deliver in humans. "It's a lot of sophisticated molecular biology," Rosenberg notes, "and most of our work is going into designing retroviruses, putting genes into cells efficiently and getting them expressed."