Head and Neck Cancer Vaccines Get Orphan Status

July 8, 2009
Kimberly Melofchik

Earlier this year, the FDA granted Orphan status to 2 vaccines designed to fight head and neck cancers. Find out how they work and trials in progress.

Two vaccines targeted at squamous cell carcinoma of the head and neck (SCCHN) recently obtained orphan drug status from the US Food and Drug Administration (FDA). The vaccines, marketed by Gliknik Inc (Baltimore, MD), are designed to target the antigens MAGE-A3 and HPV 16, which are specific to these types of cancers. The hope is that these new vaccines will stimulate the patient’s immune system.

Known as “Trojan peptide” vaccines, the vaccines are designed to enter cells with the help of a peptide sequence that transports the protein molecules through the cell membrane. The peptides are comprised of approximately 40 to 50 amino acids, far more than the number typically found in other vaccines. Once the protein molecules penetrate the cell membrane, the patient’s T cells are stimulated to recognize them as invaders and seek and destroy cancer cells containing the same proteins throughout the body.

The two vaccines were developed by Scott Strome, MD, a professor and chair of the department of otorhinolaryngology-head and neck surgery at the University of Maryland School of Medicine. His research began 7 years ago at the Mayo Clinic where he filed an Investigational New Drug Application with the FDA. In 2005 he moved to his current position at the University of Maryland and partnered with David Block, MD, MBA. Together they cofounded Gliknik Inc and received a clinical “R01” grant from the National Institute of Dental and Craniofacial Research to support clinical trials of the vaccines.

New treatments needed for devastating disease

SCCHN are cancers affecting the nasal cavity, oral cavity, sinuses, throat, pharynx, or larynx, with the oral cavity and larynx being the most common sites. Collectively, these cancers make up approximately 3% to 5% of all cancer cases in the United States, affecting approximately 43,000 people per year. SCCHN is more common in men and in people over age 50. The overall survival rate is 50%; however, if diagnosed early, the survival rate is more than 90%.

There are a number of risk factors associated with the development of head and neck cancer but certain lifestyle factors, such as smoking and alcohol consumption, are the most significant. In fact, 85% of head and neck cancers can be linked to the use of tobacco products, including smokeless or chewing tobacco. Those who use both tobacco products and alcohol are at even greater risk than people who use only one of the substances. Other risk factors include sun exposure, industrial exposure to wood or nickel dust, poor oral hygiene, Chinese ancestry, and consumption of mate, a tea-like beverage native to South America.

Head and neck cancers are difficult to treat and have a high incidence of recurrence. Current treatment options are limited and range from surgery or radiation—more often used for early stages of the disease—to chemotherapy; for later stages of disease, a combination of the 3 treatments are sometimes used. Advances in treatment options have been slow in coming, and mortality rates for SCCHN have not changed in the past 30 years. “Even with chemotherapy, radiation, and surgery, people with advanced head and neck cancer may have a limited life expectancy of 6 to 8 months,” said Dr. Block.

Because of the complex surgeries involved, head and neck cancer can be very difficult on patients. When portions of the jaw, tongue, or voice box need to be removed, for example, patients must deal with disfigurement and undergo speech therapy. Often, these patients become depressed. “Advanced head and neck cancer is an absolutely devastating disease. That is why a vaccine to treat this type of cancer would be very beneficial to patients,” Dr. Strome explained.

Ongoing clinical trial offers hope

The vaccines are currently being tested in a phase I clinical trial at the University of Maryland’s Greenebaum Cancer Center. It is fully funded by the National Institutes of Health. The study began in June 2008 and is expected to be complete by June 2012. It is the first study to use large Trojan peptide vaccines to treat patients with SCCHN.

Dr. Block advises oncologists at the practice level to “be aware that a clinical trial is ongoing that might be appropriate for their patients.” The trial is open to patients with progressive, recurrent SCCHN and those with metastatic SCCHN that is incurable by standard treatments. It is also open to those patients who elect not to receive standard therapies. Patients will receive 1 vaccine dose every 2 weeks for 8 weeks, or a total of 4 vaccine doses. Doses will be 500 mg, 1000 mg, or 1500 mg, depending on the time of enrollment.

“While the clinical impact of our vaccine is too early to assess, it is gratifying to think that we have restored hope in some patients and given them the tools to fight back against their cancers,” concluded Dr. Strome.