DNA Vaccine Provokes Immune Responses in HPV-Related Head and Neck Cancer Cases

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A therapeutic vaccine can boost antibodies and T cells, helping them infiltrate tumors and fight off head and neck cancer related to the human papillomavirus (HPV), reports the Abramson Cancer Center of the University of Pennsylvania. In its tests of the immunotherapy approach in two groups of patients with advanced head and neck squamous cell carcinoma (HNSCCa), 86% showed elevated T cell activity.

This study is the first to show that the vaccine can help immune cells infiltrate tumors, the researchers report. It also describes a patient who received the vaccine in the trial, developed metastatic disease seven months later, was treated with anti-PD-1 immunotherapy, and has been in remission for more than two years.

HNSCCa develops in the mucous membranes of the mouth and throat. Smoking and tobacco use are known causes, but cases related to HPV infection are among the fastest growing cancer types. A sexually transmitted disease, HPV is so common that the Centers for Disease Control and Prevention says that almost all sexually active adults will contract it at some points in their lives and that 70% of all head and neck cancers in the United States are now HPV-related.

While there are many types of HPV, the HPV-16 and HPV-18 subtypes are most commonly associated with cancer. Many patients with this type of HNSCCa have good outcomes for treatment that includes surgery or chemotherapy and radiation. For patients who don’t respond to treatment or who develop metastatic disease, anti-PD-1 therapy is approved but only helps about 15% of patients. 

“We wanted to know if this vaccine can boost the immune systems of patients with HPV-related head and neck cancer, potentially opening the door for better response rates to other existing therapies, and our findings show that we can,” said the study’s lead author, Charu Aggarwal, MD, MPH, assistant professor of hematology-oncology at Penn’s Perelman School of Medicine. 

Other preventive HPV vaccines are recommended for girls and boys. The vaccine used in this clinical trial is different from the preventive vaccines, which can prevent but cannot treat cancer. The vaccine in this study, MEDI0457, is a DNA vaccine that can have a therapeutic benefit. 

Researchers gave four doses of MEDI0457 to 21 patients separated into two different groups. One group received a dose before surgery, followed by three doses after surgery. The second group received four doses following chemotherapy and radiation. Eighteen of the 21 patients showed elevated T cell activity that lasted at least three months after the final vaccine dose, meaning the immune effect persisted for at least six months from the start of immunotherapy. 

Also, five tumors were biopsied both before and after one dose of the vaccine, and there was evidence of T cells reacting with antigens contained in the vaccine in all five “after” samples.

“We have not seen that kind of infiltration with just one dose of a vaccine before,” Aggarwal said. “These findings open the door for utilizing targeted immunotherapy approaches against specific cancer-causing targets like HPV.” 

The vaccine also was very well tolerated. Patients had arm pain at the site of the injection, but there were no reports of any serious side effects. The authors further described one patient who received a dose of the vaccine pre-surgery and who developed a metastatic recurrence seven months after treatment. At that point, he received the PD-1 inhibitor Nivolumab and had a complete response. Two years later, he still shows no signs of disease.

“This response suggests the vaccine may, in some manner, prime the immune system, potentially boosting the effects of subsequent anti-PD-1 therapy,” Aggarwal said.

This unique case was one of the main drivers of a Penn-led, multi-site clinical trial that is now enrolling patients. It combines the vaccine with anti-PD-1 therapy for patients with metastatic HPV-associated head and neck cancer.

“These are very important and unique results, and the next step is already underway looking at combining this vaccine with other immune therapies,” said Roger B. Cohen, MD, professor of hematology-oncology at Penn, associate director of clinical research at the Abramson Cancer Center, and coauthor of the study.

“We think our results from the single patient who is currently disease free suggest that the clinical impact of a combined vaccine and PD-1 antibody approach may be profound if it can be confirmed in ongoing and planned clinical trials,” said Cohen. 

The study, “Immunotherapy Targeting HPV 16/18 Generates Potent Immune Responses in HPV-Associated Head and Neck Cancer,” was published by Clinical Cancer Research.

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