Vinod Balachandran, oncologist: “Higher speed is important for cancer treatment, and RNA technology can make this possible” | Health and wellness

Before the advent of coronavirus vaccines, technology that controls messenger RNA was already used against cancer. RNA is synthesized in the nucleus of cells, reads the instructions written in DNA, and transmits a message to the body’s factories so that they produce all kinds of substances necessary for life. This essential molecule is now used to create drugs that tell a cell what protein to make to protect the body from a virus or eliminate a tumor.

Vinod P. Balachandran (Syracuse, USA, 44), an oncologist at Memorial Sloan-Kettering Cancer Center (MSKCC) in New York, is one of the researchers who has been working for nearly a decade to convert mRNA (messenger RNA) vaccines into useful treatments. cancer. In a video interview, he talks about recently presented results from a study involving 16 pancreatic cancer patients who, in addition to chemotherapy and a monoclonal antibody, received a personalized vaccine against each patient’s specific tumor.

In 8 patients, the vaccine induced a T-cell response against cancer, and six of them were tumor-free after three years. Of the remaining eight patients who did not have an immune response, the cancer returned in seven. Phase 2 trials are already underway, during which this personalized vaccine will be tested in approximately 260 patients.

Ask. Why did you choose pancreatic cancer as one of your goals?

Reply. Pancreatic cancer will become the second leading cause of cancer death in the United States in 2025, just one year from now. Pancreatic cancer kills more people than breast, colon, prostate or ovarian cancer, and is surpassed only by lung cancer. And it is also the leading cause of cancer deaths in the world.

This is partly because the treatment we use for pancreatic cancer is still surgery, chemotherapy and radiation. These treatments were developed many years ago and are not very effective. We urgently need new treatments. I was very interested in helping to make some progress against this deadly disease by helping patients overcome it.

TO. Part of the idea behind the therapeutic approach comes from studying the 10% of patients diagnosed with cancer who are alive five years later. What is the difference?

R. This is an idea that came to us in 2015. We asked ourselves exactly this question. We know that there are rare pancreatic cancer survivors, about 12% of patients who receive the same treatment as other patients but, amazingly, survive for a long time. We thought that by carefully studying these patients and understanding what might be different about them, we could develop treatments that would allow other patients to survive in the long term.

In 2017 we published an article in Nature in which we showed that one of the striking differences was that their tumors had about twelve times the density of CD8 T cells, highly specialized cells that protect the body from infection and cancer. This suggests that these patients may have spontaneous immune recognition of the cancer. Moreover, we were able to identify identical T cells found in the tumors spontaneously persisting in their blood more than a decade later, supporting the idea that perhaps these patients were able to mount spontaneous immune responses against their cancer. This led us to wonder if we could understand T cells being identified as foreign. By determining what they see, we could develop a strategy to train other cells in patients’ immune systems to recognize their tumors, similar to what has happened in long-term survivors.

We saw that patients’ T cells recognized that patient’s specific mutations. This meant that in order to train other patients’ immune systems to recognize cancer and create a vaccine, it had to be made individually for each patient. And at the time, we thought the best technology for this was RNA, so we approached our colleagues at Genentech and Biontech about using their RNA vaccine technology to treat cancer and testing that technology on pancreatic cancer.

TO. Why do half of patients not respond to this treatment?

R. First answer: we’re not sure. However, one possible explanation is the vaccine formula we used in this clinical study, which is administered intravenously and reaches a maximum number of lymph nodes throughout the body. This type of intravenous vaccine, unlike intramuscular vaccines, goes to the spleen, which causes a strong immune response in the patient. For pancreatic cancer, we include several operations in our routine treatment, one of which is removal of the spleen. Among those who did not respond to our treatment, there were slightly more than those who had their spleens removed before vaccination. The figure, however, was not statistically significant, so we cannot say with certainty that this is the reason, but we think it may at least be one reason why the vaccine does not work in some patients.

TO. Could the cost and time to develop a customized vaccine be a problem for it to become a treatment available to many patients?

R. Greater speed is essential to treating cancer, and RNA technology could make this possible. We are now very focused on understanding how we will use this new vaccine technology and others to train patients’ immune systems to recognize their own tumors. We want to understand whether this will be an effective drug.

TO. What are your expectations from the next stage?

R. We need to monitor the results of the first phase of the study, and a randomized phase 2 trial is open at Sloan-Kettering and around the world to test the effectiveness of the vaccine.

TO. They began working with this technology in pancreatic cancer in 2017. Since then, mRNA technology has been used around the world and in millions of people in a COVID vaccine. Did this help us learn something that could be used in cancer vaccines?

R. There are differences in the specific technologies and types of RNA delivery used in COVID vaccines and those we use in cancer vaccines. However, the public has become familiar with the concept of using an RNA vaccine and the perception of its safety, and this is encouraging the idea of ​​using these new technologies against other challenging diseases such as cancer.

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