HPV16 E6/E7 Vaccine

Taking an Idea to the Finish Line
Discovering a solution that could help treat a single form of cancer is a breakthrough, but finding a solution that could treat multiple cancers is a revolutionary feat. A team at Sanford Health Innovations has done just that – developed a vaccine targeting the cancer driving oncogenes and cells in which they are expressed, rather than the virus itself. This vaccine, HPV16 E6/E7, is now in development with a path towards clinical trials in humans.

An Idea is Born
A single virus – human papillomavirus (HPV) 16 – is responsible for the majority of head and neck, cervical and other cancers, and the genesis of a vaccine to combat HPV16-induced cancer started as an idea during a laboratory meeting. Dan Vermeer and a team, including W. Chad Spanos, MD, and Paola Vermeer, PhD, had previously discovered that HPV-positive tumors get cleared by an immune mechanism, and the team wondered if a vaccine could be created to drive immune-mediated attack of the cancer cells after tumors had formed.

Oncogenes E6 and E7 are the main contributors leading to the cellular changes that cause HPV-infected cells to become cancerous. The thought was that if the team could mutate the sites within the viral DNA responsible for these oncologic changes and express this new DNA in patients with cancer, they could potentially develop a vaccine that was safe and effective. Without inducing cellular changes, the vaccine would drive an immune response against the infected cells comprising the cancer.

A Vaccine All its Own
Current HPV vaccines are made against the coat protein of the HPV virus. This is very effective at preventing infection, but if someone has already been exposed to the virus, the vaccine would not be beneficial. Often, cellular changes as a result of HPV infection do not occur until several decades after infection, limiting current HPV vaccines from preventing cancer in a huge portion of the population. HPV16 E6/E7 vaccine is different – it works against the proteins causing the cancerous changes. Preclinical studies of the vaccine have shown an improvement in long-term survival in animal models as well as induction of strong immune responses against HPV in vivo. When used with chemotherapy or radiation, the vaccine has shown improvement in the clearance of established HPV cancer in vivo and significant reduction of tumor growth as compared with control mice.

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