In a demonstration of vaccine therapy’s potential for treating lung cancer, Dana-Farber Cancer Institute scientists and their associates report that a prototype vaccine boosted the natural immune response to tumors in a small group of patients with advanced nonsmall cell lung cancer (NSCLC). Moreover, the vaccine was found to be nontoxic and well-tolerated.
Published in the Feb. 15 issue of the Journal of Clinical Oncology, findings from the Phase I clinical trial will provide an impetus for further efforts to develop a vaccine against NSCLC, a difficult-to-treat condition that accounts for roughly 80 percent of all lung cancer cases. (Phase I trials are designed primarily to assess the safety of an experimental treatment.)
“This work represents a new approach to a vaccine for lung cancer patients,” says senior author Glenn Dranoff of Dana-Farber. “We’re still at an early stage, but the results of this study are encouraging. They offer a ‘proof of principle’ that this technique can strengthen the normal immune response to NSCLC tumors and will help form the basis for testing the vaccine in patients with earlier stage lung cancer.”
The technique was originally developed for patients with advanced melanoma, a form of cancer that begins in the skin but can be deadly if allowed to spread to other parts of the body.
The researchers created the melanoma vaccine by removing a portion of a patient’s tumor and using specially equipped viruses to insert a gene known as GM-CSF into the tumor cells. After being radiated and injected into the patient, the manipulated tumor cells began producing the granulocyte-macrophage colony-stimulating factor (GM-CSF) protein, which acted as a magnet for an immune system attack on tumor cells. As the researchers had hoped, the vaccine elicited a potent, long-lasting immune response targeted at the melanoma tumor cells – and produced only minor side effects.
In the lung cancer study, researchers developed vaccines for 34 of the 35 enrolled patients with metastatic, or spreading, NSCLC. Nine of these patients had to withdraw from the study after their disease progressed rapidly, but researchers found heightened levels of immune system cells in 18 of 25 patients whose condition could be assessed after vaccination. Tumor samples removed after vaccination showed infiltration by immune system cells and tumor cell death in three of six patients. Side effects were minor, mostly involving irritation at the site of the vaccine injection.
Two patients, the removal of whose tumors for vaccine preparation left them with no evidence of the disease, remained disease-free more than three years after vaccination. Five patients had periods of stable disease ranging from three to 33 months.
“The results demonstrate that the technique can raise antitumor immunity in some patients with NSCLC,” states Dranoff, who is also an associate professor of medicine at Harvard Medical School. “It is important to keep these findings in proper perspective: They are promising but still preliminary. More research needs to be done to see if these results occur in larger studies and in people with earlier stages of NSCLC.”
Ravi Salgia of Dana-Farber, and Thomas Lynch of Massachusetts General Hospital, were first authors of the paper. Other contributors are based at Dana-Farber, Children’s Hospital, Boston, Massachusetts General Hospital, and Cell Genesys of Foster City, Calif.