In the first clinical trial of a patient-specific cancer vaccine among lung cancer patients, researchers found that a new approach to vaccination may hold promise as a treatment for the disease. The scientists used a genetically engineered virus and cells from patients' own tumors to create individualized cancer vaccines that safely produced immune responses against cancer cells in a majority of patients. The results of the Phase I study are reported in the February 15 issue of the Journal of Clinical Oncology.

"This way of creating cancer vaccines represents a completely new therapeutic approach to lung cancer," said Dr. Glenn Dranoff, Associate Professor of Medicine, Dana-Farber Cancer Institute and Harvard Medical School, and senior author on the study. "Our study demonstrates that therapeutic lung cancer vaccines are feasible, safe, and may show clinical activity in some patients with advanced disease."

Dr. Dranoff noted that little previous research has examined vaccine strategies against lung cancer, despite the fact that the disease is the leading cause of cancer death for both men and women. Lung cancer kills more Americans than breast, prostate, and colorectal cancers combined.

This approach to fighting lung cancer was prompted by earlier studies showing that the body has a natural immune response to tumor cells in patients with non-small cell lung cancer. Although this natural response is not sufficient to overcome the cancer, laboratory research suggested that vaccination might enhance the response and increase the body's ability to fight the cancer.

To create the personalized vaccines, researchers obtained tumor tissue from 35 patients with advanced non-small cell lung cancer, most of whom already received either chemotherapy or radiation therapy. Tumor cells were infected overnight with a genetically modified adenovirus, called Ad-GM, similar to the common cold virus. The cells were then irradiated to make them harmless. Once inside the cells, this engineered virus causes the cells to produce granulocyte-macrophage colony-stimulating factor (GM-CSF), a protein that stimulates the immune system. The processed cells were then administered to the original patients by injection.

Of the 25 patients who completed at least six vaccinations, 18 experienced a clearly increased immune response against their cancer. According to Dr. Dranoff, this result is especially notable because all of the patients in the study had already received extensive treatment that limited the strength of their immune systems before the trial began.

The safety of the vaccine approach was also very favorable, especially in light of the serious toxicity of common treatments for lung cancer, such as chemotherapy and radiation. The only side effects of the vaccines were mild rash and occasional flu-like symptoms.

Although the Phase I study was not designed to measure the effectiveness of the vaccines, the researchers observed preliminary signs of clinical benefits. After a median follow-up time of 36 months, five patients showed stable disease, with the longest up to 33 months. Two additional patients who had their tumors surgically removed for preparation of the vaccine remained free of their cancer for over three and a half years. However, the researchers strongly cautioned that additional clinical trials are necessary before it is possible to tell whether most patients can benefit from this vaccination approach.

"The vaccines were very well tolerated and showed intriguing signs of clinical benefits in a minority of patients," Dr. Dranoff said. "Additional, larger clinical trials are clearly warranted." He added that Phase II trials are already underway.

"Vaccination With Irradiated Autologous Tumor Cells Engineered to Secrete Granulocyte-Macrophage Colony-Stimulating Factor Augments Antitumor Immunity in Some Patients With Metastatic Non-Small Cell Lung Carcinoma." Ravi Salgia, M.D., et al.; Dana-Farber Cancer Institute.Vol 21, No 3 (February 15) 2003, pp: 624-630.

The Journal of Clinical Oncology is the semi-monthly peer-reviewed journal of the American Society of Clinical Oncology (ASCO), the world's leading professional society representing physicians who treat people with cancer.

ATTRIBUTION TO THE JOURNAL OF CLINICAL ONCOLOGY IS REQUESTED IN ALL NEWS COVERAGE.

For the full text of any JCO article (703) 299-1014 or (212) 584-5005.

The JCO News Digest is also distributed via email. Please let us know if you would like to be added to our email distribution list.