DNA vaccine leads to immune responses in HPV-related head and neck cancers

A therapeutic vaccine can stimulate antibodies and T cells, helping to infiltrate tumors and fight head and neck cancers related to the human papillomavirus (HPV). Researchers at the Abramson Cancer Center of the University of Pennsylvania have tested the immunotherapy approach in two groups of patients with advanced squamous cell carcinoma of the head and neck (HNSCCa) and found that 86% had high T cell activity. It is also the first study to show that the vaccine can help immune cells to infiltrate tumors. The study also describes a patient who received the vaccine under test, developed metastatic disease seven months later, and then was treated with anti-PD-1 immunotherapy and has been in remission for more than two years. years. The researchers published their results in Clinical research on cancer aujourd & # 39; hui.

HNSCCa is a cancer that develops in the mucous membranes of the mouth and throat. Smoking and smoking are known causes, but the number of cases related to HPV infection – a sexually transmitted infection so common, indicates that almost all sexually active adults will contract it at some point in their lives. -Is one of the fastest growing types of cancer. The CDC estimates that 70% of all head and neck cancers in the United States are now linked to HPV. Although there are many types of HPV, HPV subtypes 16 and 18 are most often associated with cancer. Many patients with this type of HNSCCa get good results with treatment that includes surgery or chemotherapy and radiation therapy. For patients who do not respond to treatment or who develop metastatic disease, anti-PD-1 treatment is approved, but only supports 15% of patients.

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

There are other preventative HPV vaccines recommended for girls and boys. The vaccine used in this clinical trial is different from preventative vaccines, which can prevent but can not treat cancer. The vaccine in this study, known as MEDI0457, is a DNA vaccine that may have a therapeutic effect.

The researchers administered four doses of MEDI0457 to 21 patients divided into two different groups. One group received one dose before surgery, followed by three doses after surgery. The second group received four doses after chemotherapy and radiotherapy. Eighteen of the 21 patients had elevated T-cell activity that lasted for at least three months after the last vaccine dose, which means that the immune effect persisted for at least six months after the start of the test. # 39; immunotherapy. Five tumors were biopsied both before and after a dose of the vaccine, and there was evidence that T cells reacted with the antigens contained in the vaccine in the five "after" samples. "We have never seen this kind of infiltration with a single dose of vaccine before," Aggarwal said. "These findings pave the way for the use of targeted immunotherapy approaches against specific cancer targets such as HPV."

The vaccine was also very well tolerated. Patients had arm pain at the point of injection, but no serious side effects were reported.

The authors also specifically described the case of a patient participating in the trial from the cohort who received a dose of the vaccine before the surgery. This patient had a metastatic recurrence seven months after treatment, then he received the PD-1 inhibitor Nivolumab and continued to have a complete response. Two years later, he still shows no signs of illness. "This response suggests that the vaccine could, in a way, boost the immune system, potentially increasing the effects of subsequent anti-PD-1 treatment," said Aggarwal. This unique case was one of the key drivers of a multi-site clinical trial led by Penn, who is currently recruiting patients. It combines the vaccine with anti-PD-1 treatment for patients with head and neck cancer associated with metastatic HPV.

"These are very important and unique results, and the next step is already underway to combine this vaccine with other immunotherapies," said Roger B. Cohen, MD, professor of hematology-oncology at Penn and Associate Director of Clinical Research at the Abramson Cancer Center. "We believe that our findings for a single patient currently free of disease suggest that the clinical impact of a combined vaccine and anti-PD-1 antibody approach could be profound if it can be confirmed in ongoing and planned clinical trials. " Posted in Clinical research on cancer and was co-author.

Explore more:
Immunotherapy with a DNA vaccine is promising for HPV-related head and neck cancer