Vaccines as Cancer Prevention and Therapies

Rachel Cherney

Cancer is a complex set of diseases, characterized by uncontrolled growth and metastasis, destroying important organs and bodily systems. It can occur in almost any part of the body, and in most cases, it is impossible to determine how or when it will develop, certain genetically linked cancers perhaps being an exception. Because of cancers’ variability, finding cancer therapies that work for every cancer, and for every patient, is exceedingly challenging, and scientists and doctors need to look in unlikely places for creative solutions for functional cancer therapies.

Many scientists are turning to the idea of creating vaccines to fight cancer. When a pathogen enters the body, it comes into contact with certain immune system cells. These cells have a reaction to the pathogen and create antibodies (markers to detect the particular pathogen). The immune system then destroys the pathogen so our body doesn’t get an infection. The next time the pathogen enters the body, the immune system can much more quickly detect and destroy it. Vaccines work the same way, in that we intentionally introduce pathogens to our body to make our immune system stronger. However, the pathogens that we introduce to our bodies have been fixed so they can’t cause us harm. The thought behind cancer vaccines is to strengthen the patient’s immune system so the body can destroy cancer itself, rather than use surgery or chemotherapy. This occurs through educating the immune system to recognize markers of cancer, as just described with viral and bacterial vaccines.

The downfall of vaccine development is many don’t make it past clinical trials, but the ones that HAVE made it past clinical trials have been extremely successful. Hepatitis B is a virus that causes damage to and cancer in the liver, but its vaccine is extremely effective in protecting the liver. The common human papillomavirus (HPV) is also a virus, and if left untreated, results in various cancers in both men and women, particularly cervical cancer. However, the HPV vaccine is almost 100% effective against HPV and the CDC recommends that all kids should get the HPV vaccine around the age of 12. Just this week, the FDA approved the HPV vaccine for people up to 45 years of age, greatly expanding the number of people eligible. However, these are preventative cancer vaccines that make sure a pathogen can’t eventually cause cancer. So how do we create and use vaccines for cancers that weren’t caused by a pathogen?

Viral_Tegument
General virus structure

A few years ago, the Zika virus emerged from South and Central America. Since its appearance, Zika has been linked to microcephaly (abnormally small head) and other abnormalities in the offspring of affected pregnant women because it attacks and disrupts the function and development of brain cells in the fetus. Due to its severity, scientists around the world worked hard to find effective vaccines. Several vaccines have since been generated that are safe and efficient to use in mice and primates, and some have moved into clinical trials in humans. However, answers to problems can come from unexpected places. In a recently published paper in mBio by the American Society for Microbiology, a group from China assessed the ability of a newly developed Zika vaccine to eliminate human glioblastoma tumors and found that the vaccine preferentially attacked the glioblastoma tumors without causing harm to the normal brain tissue, effectively destroying the tumors.

Glioblastoma is the most aggressive, and the deadliest type of brain cancer. It was most recently in the news because former senator John McCain developed glioblastoma and stopped treatment, resulting in his passing. Most treatments for glioblastoma don’t work because it grows in many locations throughout the brain (not just one tumor), so surgically removing them is hard. In addition, a subpopulation of glioblastoma cells, known as glioma stem cells (GSCs) are resistant to chemotherapy and radiation and can self-renew, meaning tumors often regenerate quickly after treatment. The self-renewing properties of GSCs are similar to the fetal brain cells the Zika virus attacks. This similarity led the Chinese scientists to the idea that maybe a Zika vaccine could decrease the growth and severity of GBM. They developed a vaccine that required engineering (changing the DNA) of the Zika virus so that it no longer has its virulence, but still has its oncolytic (cancer-killing) properties.

The scientists then tested their engineered Zika vaccine in mice to see whether it would result in Zika-like symptoms or death – meaning the vaccine was unusable. 18 days after injecting mice with the vaccine, the mice did not die or have any Zika-like symptoms, and the vaccine stayed in the brain; it didn’t travel or have any effects on other parts of the body. These tests demonstrated the safety of the vaccine on the body, and the scientists then began to test the vaccine on human GBM tumors transplanted into mice. They saw that the vaccine infected and destroyed the GSCs, but not other normal brain tissue. The vaccine destroys the cells by activating cell death pathways, essentially telling the cell to die. Although more tests will need to be done before this particular candidate vaccine is tested in humans, this study is extremely promising in the progress towards a therapy for GBM.

Works Discussed

  1. Qi Chen, Jin Wu, Qing Ye, Feng Ma, Qian Zhu, Yan Wu, Chao Shan, Xuping Xie, Dapei Li, Xiaoyan Zhan, Chunfeng Li, Xiao-Feng Li, Xiaoling Qin, Tongyang Zhao, Haitao Wu, Pei-Yong Shi, Jianghong Man, Cheng-Feng Qin. Treatment of Human Glioblastoma with a Live Attenuated Zika Virus Vaccine Candidate. mBio, 2018; 9 (5) DOI: 10.1128/mBio.01683-18
  2. Guo C, Manjili MH, Subjeck JR, Sarkar D, Fisher PB, Wang X-Y. Therapeutic Cancer Vaccines: Past, Present and Future. Advances in cancer research. 2013;119:421-475. doi:10.1016/B978-0-12-407190-2.00007-1.

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