As published in the June 26 online issue of the New England Journal of Medicine and discussed in the accompanying editorial, physician-scientists at Duke University Medical Center in Durham, NC, have devised a new and potentially breakthrough strategy for treating recurrent grade IV malignant glioma, the same brain tumor that tragically ended the life of Senator Edward Kennedy and is threatening the life of Senator John McCain.

The scientists injected a genetically engineered version of the poliovirus, the same virus that formerly caused child paralysis, and peaked in the US in 1952 with almost 52,000 reported cases and more than 3,000 deaths.  The iron lung machines collecting dust in the hallways of the Philadelphia General Hospital served as a stark reminder when I was a medical student at PENN.

As stated in UptoDate, "Immunization against poliovirus infection represents one of the world's great medical achievements.  The last cases of paralytic poliomyelitis in the United States occurred during a small outbreak in an unvaccinated religious community in 1978 and 1979.  All nations in the Western Hemisphere, Europe, Southeast Asia, and the Pacific Region are free of poliomyelitis. As of February 2018, poliovirus remains endemic in Nigeria, Pakistan, and Afghanistan" and it remains a major objective of the World Health Organization to eradicate polio worldwide by 2019, using the same population immunization methods that wiped out smallpox worldwide by 1979.   CDC recommends polio vaccination at each of the following ages: 2 months, four months, 6-18  months, and 4-6 years old.  Smallpox vaccination is no longer necessary because smallpox is extinct.

The virus used in the current polio vaccine was developed by Dr. Jonas Salk and involves inactivating ("killing") the virus with formaldehyde.   Dr. Maurice Hilleman of the Merck Research Laboratories played a key role in manufacturing the vaccine for widespread use.

You may recall there was a second polio vaccine developed by Dr. Albert Sabin.  Sabin emigrated to the United States from Russia at age 15, graduated from high school in Paterson, NJ, and received his undergraduate and medical degrees from NYU. He served in the US Army Medical Corps in WWII.  While working at the University of Cincinnati College of Medicine,  Sabin developed a vaccine that was still infectious but could not cause disease.  It is referred to as a "live, attenuated" vaccine.  The Sabin vaccine is still used in developing parts of the world because it is given orally and is ideal for mass immunizations to isolate outbreaks.  This was the vaccine I received as a child.  

The Sabin vaccine is no longer used in developed nations because it is known to rarely cause vaccine-associated paralysis.

While we no longer use the Sabin vaccine in the US, it taught us a valuable lesson: viruses can be modified to infect cells and engender a protective immune response without causing disease. This was essentially the approach used by the scientists at Duke. They re-engineered the poliovirus so that, once injected directly into the glioblastoma, it bound, entered and killed tumor cells without multiplying, spreading, and damaging normal cells. Moreover, infection of tumor cells is believed to induce an immune response allowing killer T cells ( cytotoxic T lymphocytes) to seek out and destroy glioblastoma cells that were never infected by the virus. The MRI images are dramatic showing decimated tumors!

While once a scientific backwater, tumor immunology has matured to the point where lives are being prolonged if not saved.  As discussed in previous issues, CAR-T is a breakthrough technology, developed by Carl June and colleagues at the University of Pennsylvania School of Medicine, that uses the patient's own engineered T cells to kill tumor cells.  Moreover, monoclonal antibodies directed against PD-1 and PD-L1 are now coming into widespread use for the treatment of lung cancer and a variety of other difficult-to-treat cancers.  Harnessing the power of the immune system to kill tumors has given new meaning to the phrase, " Host Defense", and stands to revolutionize the field of oncology.