Neuro-oncologist Dr. Santosh Kesari talks about the difficulties of treating brain cancer and the promise that mRNA vaccines hold.

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Around 40% of us are likely to develop cancer at some point in our lives. Modern medicine has seen considerable advances in cancer treatments, which has contributed to a steady decline in cancer deaths in the United States over the past 30 years.

Despite this, around 10 million people worldwide die each year from cancer.

Brain cancers are notoriously difficult to treat, in part because of the challenges of delivering drugs into the brain. Only around 36% of people with malignant brain cancer survive more than 5 years.

Could mRNA vaccines hold the answer?

To find out, I spoke to Dr. Santosh Kesari, a neurologist and neuro-oncologist. Dr. Kesari is the director of Neuro-oncology at Pacific Neuroscience Institute and a professor in the Department of Translational Neurosciences and Neurotherapeutics at Saint John’s Cancer Institute, both in Santa Monica, CA.

We talked about the challenges of treating brain cancer and why Dr. Kesari thinks that mRNA vaccines have the potential to impact cancer treatment on a global scale.

To hear more about how cancer develops, how experts are developing tailored treatments for individual patients, and how Dr. Kesari sees mRNA vaccines and the future of cancer therapies, listen to the accompanying podcast here.

This podcast is also available on Spotify, Apple Podcasts, and other platforms.

To start our conversation, I asked Dr. Kesari to share the biggest challenge he faces when treating his patients.

“One of the difficult things and the reason we haven’t made as much progress in brain cancer, and actually all brain disorders in general, is the blood-brain barrier,” he explained.

The blood-brain barrier comprises a lining of cells around the blood vessels in the brain. It prevents big molecules and pathogens from entering the brain.

“It’s really an evolutionary protective mechanism. We don’t want all the things that the rest of our body sees to go into the brain and cause neurological problems, including infections [by] viruses, bacteria, etc.,” Dr. Kesari said.

Yet, this also means delivering drugs into the brain is difficult.

“Probably the most critical challenge that we have to deal with all brain diseases is getting drugs into the brain.”

Despite this hurdle, Dr. Kesari is hopeful. He explained that scientists and pharmaceutical companies have a long history of working on solutions to overcome such challenges.

Messenger RNA (mRNA) vaccine technology has become almost a household name in the past year. Two COVID-19 vaccines, by Pfizer-BioNTech and Moderna, employ this technology.

But mRNA vaccine research also has strong roots in the cancer field.

Dr. Kesari explained where he sees the potential for mRNA vaccines in cancer. “The great thing about mRNA [vaccines] are the manufacturing, scalability, and cost,” he said.

He used COVID-19 as an example. Scientists from China published the molecular code for the SARS-CoV-2 virus in January 2020. This allowed scientists and pharmaceutical companies with mRNA vaccine development expertise to initiate work on creating novel mRNA vaccines specifically designed to match the virus.

“It’s really built upon decades of research and informatics because understanding what’s a good vaccine [and] what’s not a good vaccine at the protein level, and then translating to the mRNA level has been built over many decades,” Dr. Kesari explained.

He drew a parallel between COVID-19 and the challenges he faces when treating patients with brain cancer.

“Brain tumors to me is COVID every day [and] has been for 20 years, meaning there’s such an urgent need; these patients die rapidly. There are no good treatments. Obviously, COVID is a pandemic, but on a daily basis to the individual patient — we deal with those sorts of life threatening issues all the time.”

Dr. Kesari sees great potential in mRNA vaccines as part of a wider arsenal to treat his patients. The speed and ease of manufacturing make this particular vaccine platform an attractive candidate for novel treatments.

One of the reasons our bodies struggle with cancer is because cancer cells are good at hiding from our immune system. They can mask as ordinary cells, leaving the immune system blind to their presence.

The past decade has seen a flurry of scientific breakthroughs in restoring the immune system’s ability to find and attack cancer cells. This type of treatment is called immunotherapy.

“It’s been an interesting shift from these traditional approaches of surgery, radiation, [chemotherapy], to now immunotherapy being added and leading the treatments for many cancers,” Dr. Kesari said. “For brain [cancer] though, we’ve studied many of these. And while there are hints of activity in the brain, we still have a long way to go. There’s nothing approved in the brain in terms of immunotherapies.”

Cancer vaccines are one form of immunotherapy, along with the likes of checkpoint inhibitors, chimeric antigen receptor T-cell therapy, immune system modulators, and monoclonal antibodies.

The purpose of a cancer vaccine is to get cancer cells to make and display proteins on their cell surface that alert the immune system to their presence, taking away their power of going undetected.

“I think this mRNA technology can be used for any cancer, including brain cancers,” Dr. Kesari commented. The key to developing vaccines is gathering information on the target.

“When we see a patient with cancer nowadays, we’re sequencing every tumor so that we can figure out what all the mutations are.”

Knowing exactly which mutations an individual’s cancer carries could allow scientists to develop mRNA vaccines specific to their particular cancer. Customizing treatment in this way, whether for cancer or other diseases, is known as personalized medicine.

The traditional approach to cancer is to use surgery, radiation, and chemotherapy, with the addition of immunotherapy over the last decade.

Dr. Kesari and his colleagues are working at the forefront of developing personalized treatments for their patients and are incorporating immunotherapy differently.

“After chemotherapy, the immune system just isn’t strong enough for immunotherapy to work. So our idea was to [use immunotherapy] neoadjuvantly, meaning before radiation and chemo,” he explained.

His research in this area so far has centered around using two checkpoint inhibitor immunotherapy drugs.

“Some patients have [had] remarkable responses for many years. Now, I wish I could say it was a high percentage, but it’s a start. Going forward, we want to combine it with the vaccines that we discussed. And we want to do it personalized as well,” he added.

This approach could see the development of a personalized mRNA vaccine specifically tailored to a patient’s tumor, based on the molecular analysis performed at the time of surgery. Within a few weeks, treatment with the vaccine in combination with other immunotherapies would commence.

Dr. Kesari uses the term “PIN” to describe this approach, which stands for Precision Immunotherapy in the Neoadjuvant Setting clinical trial. He shared some of his experiences with this approach so far.

“We’ve seen [successes] in various patients on our clinical trial. Not a super high response rate, but nonetheless, for the patients who responded, it’s amazing. Several patients out over 2–3 years not having had to do radiation. So it is quite promising. We want to build upon that.”

But does Dr. Kesari see this working on a global scale?

“Absolutely,” he said. “I think research always starts in one place. And as we show that it works and get the approvals, you know, [it] expands and expands. I think the mRNA vaccines are kind of a low cost approach. And if we can make vaccines work using that technology, [it] will absolutely help in terms of cost and adoption, and getting it to all the needy people around the world.”

“We’re very excited [about] using new technologies and using them to prove that something works, but also to make sure once it’s approved that everyone gets access to it.”

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