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How a new mRNA vaccine could use the body’s immune system to fight cancer

Posted on December 16, 2021December 20, 2021

When Omar Rodriguez finishes chemotherapy in February, he will return to the hospital for a dose of an mRNA vaccine. But it won’t be for Covid-19.

Rodriguez, 47, of Edinburg, Texas, was diagnosed with stage 3 colon cancer this summer. He has already had surgery to remove the tumor, but even after chemotherapy, his doctor told him there’s still a 70 percent chance his cancer will return in the next five years.

Rodriguez will be among the first people in the U.S. to receive a novel, personalized vaccine that harnesses the same mRNA technology used in Pfizer-BioNTech’s and Moderna’s Covid vaccines. This time, the vaccine won’t teach the body to target the coronavirus, but cancer cells, instead. 

The vaccine is being made by BioNTech, the German pharmaceutical company that partnered with Pfizer last year to produce the first Covid vaccine to be authorized for emergency use in the U.S. The company is studying the experimental vaccine in a phase 2 clinical trial; Rodriguez is one of the participants.

BioNTech had its sights set on an mRNA vaccine long before the coronavirus swept the globe last year. The company was founded 13 years ago with the goal of developing cancer therapies, said its CEO, Dr. Uğur Şahin. 

The German company isn’t alone: Scientists around the world had been working to develop mRNA vaccines for decades before the coronavirus pandemic pushed the technology into the mainstream. The seemingly endless possibilities include treating or curing chronic diseases, including HIV and cancer. 

Strands of mRNA, or messenger RNA, are tiny snippets of genetic code that tell the body how to build proteins, essential building blocks of every cell in the body. 

The idea behind an mRNA vaccine — whether for Covid or for cancer — is to use the genetic material to train the immune system to target a specific protein. For the coronavirus, it’s the spike protein on the surface of the virus. For cancer, it could be a protein on the surface of a tumor cell. Once the immune system learns to recognize the protein, it can create antibodies or T cells that fight and destroy it, along with the cells that carry it.

A researcher prepares a fine tissue section from a patient’s tumor sample to investigate the tumor’s molecule makeup.BioNTech

“Messenger RNA is a unique chemical entity,” said Yizhou Dong, an associate professor of pharmaceutics and pharmacology at Ohio State University. Dong is not involved with the BioNTech vaccine. “It’s a very simple code that you can apply to any protein or peptide of interest, so it can be very versatile.”

Covid has pushed mRNA technology forward an incredible amount, said Anna Blakney, an assistant professor of biomedical engineering at the University of British Columbia who specializes in mRNA biotechnology. 

“We now know it’s both advantageous and safe,” said Blakney, who also isn’t involved with the BioNTech research. “I don’t think it’s immediately going to solve all these problems, but I do think there are areas that can really take the technology to the next level, and that’s really promising.”

Fighting cancer relapse

BioNTech chose to target colorectal cancer for a potential vaccine because of the disease’s relatively high rate of relapse. 

Colorectal cancer has been on the rise among people younger than 65 for the past decade, according to the Centers for Disease Control and Prevention. And a study led by the American Cancer Society estimated that people born in 1990 have double the risk of developing colorectal cancer in their lifetimes compared to people born around 1950, when risk was at its lowest.

With current treatments, about 30 percent to 40 percent of patients diagnosed with colorectal cancer will have a relapse about two or three years after surgery that’s caused by stray cancer cells that have moved elsewhere in the body, Şahin said.

“The question is if we add a vaccine, can we prevent these relapses?” Şahin said. “We believe the vaccine could be in a position to do that.”

A researcher looks at stained tissue from a patient’s tumor sample.BioNTech

The novel vaccine uses proteins unique to people’s tumors to train their immune systems to recognize cancer cells and then fight and hopefully kill the cells.  

“Instead of using more traditional chemotherapy, it’s now trying to get the body’s own immune system to fight the cancer,” said Dr. Scott Kopetz, a professor of gastrointestinal medical oncology at the University of Texas MD Anderson Cancer Center, who is leading the phase 2 clinical trial of the vaccine in the U.S. 

Additional trials are enrolling patients in Belgium, Germany and Spain, for a total of 200 people. 

To join the trial, patients must have tiny fragments of cancer DNA in their blood, even after they have undergone surgery or chemotherapy, said Dr. Liane Preußner, the vice president of clinical research at BioNTech. Detecting the cancer fragments in the blood is referred to as a liquid biopsy.

“Even though they are tumor-free on CT scans after the surgery, they probably have a very tiny amount of the tumor remaining in the body, making them at risk of an early disease recurrence,” Preußner said, adding that the goal is to intervene early with a targeted mRNA vaccine that could kill the remaining cells early on and prevent recurrences.

A new frontier of personalized medicine

When Rodriguez, the cancer patient from Texas, finishes his course of chemo early next year, doctors will do a liquid biopsy to check for circulating tumor DNA. 

If they find it, cancer cells from his tumor will be shipped off to BioNTech’s factory in Mainz, Germany. There, cancer cells from people like Rodriguez are analyzed for mutations specific to the patients and encoded in mRNA strands that go into tailor-made vaccines. 

The vaccine can target up to 20 mutations, and the whole process, from tumor biopsy to shot, takes around six weeks, Preußner said. “We need to screen the tumor, looking for the mutations. Then it takes a couple of days to manufacture the vaccine, to do the quality control, and then of course to ship it back to the hospital.”

A major advantage of mRNA therapies is the breakneck speed at which tailored treatments can be designed and produced. 

“It really only takes days to design a new mRNA vaccine,” Blakney said. “As long as you know the protein you need to code, you just type that into software and order that DNA.” 

Those enrolled in the four-year clinical trial will receive one infusion of the vaccine a week for six weeks to mount immune responses. After that, they will switch to a biweekly schedule and then every couple of weeks for about a year. 

The process, which isn’t unique to colon cancer, holds the potential for a wide range of recurrent cancers. A phase 2 clinical trial run by BioNTech partner Genentech is investigating a tailored mRNA for patients with melanoma. 

“It’s a very promising field, and we’re still at the beginning of the possibilities,” said Dong of Ohio State University. “There will only be more as we continue to better understand cancer biology.”

Follow NBC HEALTH on Twitter & Facebook. 

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