Goal is to stimulate the body’s immune system to seek out and destroy tumor cells
University of Maryland researchers have begun testing “Trojan peptide” vaccines to treat squamous cell carcinoma, a common type of head and neck cancer. The goal is to learn whether the vaccines, which target specific proteins made by tumors, can stimulate the body’s immune system to destroy the cancer.
Made from peptides, or fragments of proteins found in select tumor cells, the vaccines being used in this Phase I clinical study are designed to slip into cells with the help of a “chaperone” that carries the bulky protein molecules through dense cell membranes, much like a “Trojan horse” bringing soldiers behind enemy lines before a surprise attack.
“We hope that these vaccines will stimulate the patients’ T cells, or immune cells, to recognize the proteins as invaders and seek out and kill the cancer cells throughout the body that produce the same proteins,” says Scott E. Strome, M.D., professor and chairman of the Department of Otorhinolaryngology-Head and Neck Surgery at the University of Maryland School of Medicine and the lead investigator of the study.
Both vaccines being tested target proteins linked to squamous cell cancers of the head and neck, most commonly seen in the mouth, throat and other parts of the upper digestive tract.
The proteins are human papillomavirus (HPV) 16 and MAGE-A3. HPV 16 is also linked to cervical cancer.
Dr. Strome, who helped to develop these unique peptide vaccines, says that the vaccines are experimental and it is not known yet if they will reduce or eliminate patients’ tumors. Researchers hope that the vaccine therapy will improve the survival rate and quality of life for patients.
Cancers of the head and neck – including those of the throat, mouth, voicebox, sinuses, salivary glands and skin – are often difficult to treat and have a high risk of recurrence. Treatments include surgery, chemotherapy and radiation therapy.
More than 40,000 people in the United States are diagnosed each year with head and neck cancer, and about half will die of the disease. Smoking has been linked to some cancers, but physicians are seeing an increase in this type of cancer in people who do not smoke.
“If patients have finished radiation treatment and chemotherapy and no more surgery can be performed, they are out of standard options,” Dr. Strome says. “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.”
He says that these vaccines are very different and more complex than traditional peptide vaccines. The peptides in these vaccines are comprised of approximately 40 to 50 amino acids, compared with much smaller numbers of amino acids in other vaccines. Researchers believe these larger peptides may trigger a stronger, two-pronged response by the body’s immune system, according to Dr. Strome. The vaccines also contain a peptide sequence that helps to transport the proteins into cells that “present” them to the body’s immune system.
“We have used the latest scientific knowledge to design these vaccines. We hope that they will help patients, which is always our goal, but we also know that the knowledge we gain from this study may in the end help us to design even better vaccines. This is the first time that these very large Trojan peptide vaccines have been used to treat patients,” Dr. Strome says. He notes that the University of Maryland School of Medicine is seeking to patent the vaccines.
Dr. Strome expects to enroll up to 90 patients over the next two to three years in the clinical trial, which is funded by the National Institutes of Health. The study is open to patients with advanced disease who have exhausted their treatment options as well as patients who choose not to receive standard therapies.
To be eligible for the trial, patients must be likely to develop an immune response to the vaccines. Researchers will determine that by testing blood and tissue samples. One group will receive the HPV 16 vaccine, another group will get the MAGE-A3 vaccine and a third group will receive both vaccines. They will also receive two immune-system stimulants, GM-CSF and Montanide ISA 51, to bring cancer-fighting white blood cells to the injection site.
Patients will receive four vaccinations over four months and may be eligible to receive another four injections if their tumors are responding to the treatments, Dr. Strome says. Researchers will use PET/CT scans and biopsies to determine whether the therapy is working.
Others involved in the development of the vaccines are Esteban Celis, M.D., Ph.D., of the Louisiana State University Medical School; Steven F. Dowdy, Ph.D., of the University of California, San Diego School of Medicine; and Soldano Ferrone, M.D., Ph.D., of the Roswell Park Cancer Institute in Buffalo, N.Y.