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Vaccination as a therapy: Experimental vaccine against cervical cancer successfully tested in mice

No. 03 | 16/01/2019 | by Eck

Scientists from the German Cancer Research Center (DKFZ) have developed an experimental vaccine to fight cervical cancer caused by human papillomaviruses (HPV). This has already been accomplished successfully in mice. Tumors regressed in half of the vaccinated animals. The scientists' goal is to develop a therapeutic vaccine for people who are already suffering from cancer or cancer precursors and, thus, no longer benefit from preventive vaccination.

Computer-generated simulation of a HPV
© DKFZ

Cervical cancer is the third most frequent cancer in women worldwide. It is caused by human papillomaviruses (HPV) that infect cells of the cervical mucosa and cause them to grow out of control. Infection with HPV can also cause anal cancer and cancers of the oral cavity. Preventive vaccines are available for preventing infection with the cancer-causing viruses. However, this HPV vaccination is ineffective in people who have already been exposed to the virus. In addition, vaccination rates are low. Despite existing vaccination recommendations – by now also for boys – by the Standing Committee on Vaccination (STIKO), only half of the girls aged 17 in Germany have been vaccinated.

"Our goal is to develop a therapeutic vaccine for treating individuals that have already contracted HPV infection and may already have developed HPV-induced cancer or precancerous lesions," said Angelika Riemer from the German Cancer Research Center (DKFZ). "A therapeutic vaccine stimulates the immune system and causes it to attack and kill infected or transformed cells."

One of the major differences between preventive and therapeutic vaccines is the time of vaccination: A preventive vaccine is only effective if it is administered before an infection has taken place. By contrast, a therapeutic vaccine is used to treat already existing infections and their consequences.

Another difference between preventive and therapeutic vaccinations is apparent in the immune system's response. Following a preventive vaccination, the body develops antibodies that protect it from future infection with the pathogen. A therapeutic vaccination, however, activates cytotoxic T cells. These immune cells are capable of recognizing minute molecular structures of the papillomaviruses, called epitopes, which are displayed on the surface of infected cells or cancer cells, thus identifying them as suspicious, and eliminating these cells.

Riemer and her colleagues have already been able to show in mice that their experimental vaccine is effective against HPV-associated cancers. "The tumors regressed completely in half of the vaccinated animals," reported the DKFZ researcher.

The key component of the vaccine are the epitopes which HPV-associated tumors also exhibit on their surface. Following vaccination, these protein structures are carried into the lymph nodes. "This is particularly efficient in order to trigger an immune response because this is where all immune cells responsible for an immune response are present," said Riemer.

In this case, the cytotoxic T cells are crucial. When they come into contact with the epitopes from the vaccine, this is a signal for them to start searching the rest of the body for cells which also display these recognition molecules. If the cytotoxic T cells encounter cancer cells carrying these HPV epitopes on their surface, they destroy them.

The therapeutic vaccine against cervical cancer and other HPV-associated cancer types is currently still in the preclinical development stage. A couple of hurdles must be overcome before it will be possible to use it in humans. "The effectiveness of the vaccination must be increased," said Riemer.

Experience from the development of therapeutic vaccines against other cancers has shown that a vaccine is in some cases more effective if it contains more than one recognition molecule. "However, in our first experiment in mice it was the opposite," Riemer reports. "Maybe for HPV tumors it is better to use only one recognition molecule which is a really good one. But we need further investigations to verify this."

Sebastian Kruse, Marleen Büchler, Philipp Uhl, Max Sauter, Philipp Scherer, Tammy C.T. Lan, Samantha Zottnick, Alexandra Klevenz, Ruwen Yang, Frank Rösl, Walter Mier & Angelika B. Riemer: Therapeutic vaccination using minimal HPV16 epitopes in a novel MHC-humanized murine HPV tumor model
OncoImmunology 8:1, e1524694, DOI:10.1080/2162402X.2018.1524694

The German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) with its more than 3,000 employees is the largest biomedical research institution in Germany. At DKFZ, more than 1,300 scientists investigate how cancer develops, identify cancer risk factors and endeavor to find new strategies to prevent people from getting cancer. They develop novel approaches to make tumor diagnosis more precise and treatment of cancer patients more successful. DKFZ’s Cancer Information Service (KID) provides individual answers to all questions about cancer for patients, the general public, and health care professionals. Jointly with partners from Heidelberg University Hospital, DKFZ runs the National Center for Tumor Diseases (NCT) located in Heidelberg and Dresden, and, also in Heidelberg, the Hopp Children’s Cancer Center (KiTZ). In the German Cancer Consortium (DKTK), one of six German Centers for Health Research, DKFZ maintains translational centers at seven university partnering sites. Combining excellent university hospitals with high-profile research at a Helmholtz Center at the NCT and DKTK sites is an important contribution to the endeavor of translating promising approaches from cancer research into the clinic in order to improve the chances of cancer patients. DKFZ is a member of the Helmholtz Association of National Research Centers, with ninety percent of its funding coming from the German Federal Ministry of Education and Research and the remaining ten percent from the State of Baden-Württemberg.

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