DNA Vaccine Leads to Immune Responses in HPV-Related Head and Neck Cancer in Small Study
Charu Aggarwal, MD, MPH
A therapeutic vaccine may boost antibodies and T cells, helping them infiltrate human papillomavirus (HPV)-related head and neck cancer tumors. Researchers from the Abramson Cancer Center of the University of Pennsylvania tested the immunotherapy in two groups of patients with advanced head and neck squamous cell carcinoma (HNSCC) and found 86% showed elevated T-cell activity. It is the first study to show that the vaccine can help immune cells infiltrate tumors. Moreover, 1 patient who received the vaccine on the trial developed metastatic disease 7 months later, was then treated with anti–programmed cell death protein 1 (PD-1) immunotherapy, and has been in remission for more than 2 years. These findings were published by Charu Aggarwal, MD, MPH, Assistant Professor of Hematology-Oncology at Penn’s Perelman School of Medicine, and colleagues in Clinical Cancer Research.
The number of cases of HNSCC related to HPV infection is among the fastest growing cancer types. The Centers for Disease Control and Prevention estimates 70% of all head and neck cancers in the United States are now HPV-related. The HPV 16 and 18 subtypes are most commonly associated with cancer. Many patients with this type of HNSCC have good outcomes from treatment that includes surgery or chemotherapy and radiation. For patients who don’t respond to treatment or who develop metastatic disease, ant–PD-1 therapy is approved, but only shows activity in 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 Dr. Aggarwal.
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 neoadjuvant dose, followed by three adjuvant doses. The second group received four doses following chemotherapy and radiation.
Eighteen out of the 21 patients showed elevated T-cell activity that lasted at least 3 months after the final vaccine dose, meaning the immune effect persisted for at least 6 months from the start of immunotherapy. 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,” Dr. Aggarwal said. “These findings open the door for utilizing targeted immunotherapy approaches against specific cancer causing targets like HPV.”
The vaccine was also well tolerated. Patients had arm pain at the site of the injection, but there were no reports of any serious side effects. The authors also specifically described the case of one patient from the cohort that received a neoadjuvant dose of the vaccine. That patient developed a metastatic recurrence 7 months after treatment, at which point he received nivolumab (Opdivo) and went on to have a complete response. Now, 2 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,” Dr. Aggarwal said. ■