There’s a new weapon in the cancer fighting arsenal.
In a joint statement, biotech companies Moderna and Merck announced this week that a new experimental vaccine combined with the drug Keytruda kept the skin cancer known as melanoma from spreading or coming back longer than Keytruda alone, in a trial that included 1,137 patients. Both treatments enlist the patient’s own immune system against the cancer — an approach known as immunotherapy.
“It is very promising,” Mansoor Amiji, professor of pharmaceutical and biomedical sciences at Northeastern University’s Bouvé College of Health Sciences said, explaining that the vaccine can delay when the cancer reappears and help patients live longer.
The implications could reach far beyond melanoma.
Worldwide, new cancer cases are expected to reach 33 million by 2050, according to the National Cancer Institute, a federal research agency. Surgery, radiation and chemotherapy remain mainstays in treatment, but doctors are increasingly turning to immunotherapy to supplement current methods. According to the Cancer Research Institute, a non-profit focused on advancing immunotherapy, this kind of treatment has already more than doubled the five-year survival rates for metastatic melanoma.
So how does the new vaccine fit into the picture? And is it as promising as it sounds?
Amiji and Stephen Hatfield, a professor at Bouvé College of Health Sciences and director of the pharmaceutical and biomedical sciences graduate program share their thoughts with Northeastern Global News.
How does a cancer vaccine work?
“We always think about administering vaccines in healthy individuals with the hope that it will prevent disease from those. But when it comes to cancer, it’s more of a therapeutic strategy,” Amiji said.
Vaccines give the immune system a preview of a threat, teaching it to recognize proteins called antigens found on the surface of foreign cells. A type of immune cell known as B-cells respond by producing antibodies. If antigens are the locks that need to be targeted, antibodies function as keys that bind to them, disabling the invading cell or flagging it for destruction by other immune cells. The immune system remembers the target and responds quickly the next time.
Some vaccines rely on messenger RNA, or mRNA, which is an abridged version of DNA instructions for building proteins. Instead of teaching the body to recognize pathogens, the way regular vaccines do, mRNA vaccines teach the body to make antigens from scratch.
Cancer vaccines use this strategy against tumors, Hatfield explained.
These vaccines contain mRNA carrying instructions for making specialized abnormal proteins that are a result of mutations in cancer cells. The cells make copies of these proteins, known as neoantigens, thereby providing the immune system with a molecular mugshot of what to hunt down.
“It trains our immune system to recognize the tumor as being different from healthy tissue,” Amiji said.
Northeastern professor Stephen Hatfield says personalized cancer vaccines show promise by activating T-cells against multiple targets. Unique to a patient’s tumor, those targets are different abnormal proteins that distinguish cancer cells from healthy ones. Photo by Alyssa Stone/Northeastern University
What makes the vaccine personalized?
Scientists start with a biopsy, Hatfield said, removing a bit of cancerous tissue from a patient. They then compare the genetic material of tumor cells with healthy tissue, flagging mutations in the cancerous tissue that produce neoantigens.
Every tumor has a unique mix, Amiji explained. “So if I was a patient, my signature may be slightly different from someone else’s,” he added.
The Moderna-Merck vaccine includes mRNA for up to 34 possible neoantigens unique to the patient’s tumor, according to the companies.
Once injected, the mRNA prompts cells to produce copies of those targets, Hatfield explained. That activates immune system ground fighters known as T-cells. They multiply and fan out, looking to directly attack cells displaying the same neoantigens.
“Now you have an army of T-cells that circulate and try to find that particular antigen,” Hatfield explained. “The only place, hopefully, that they find that is in the tumor,” he added.
Why is the second drug, Keytruda, an important component?
To kill a cancer cell, T cells have to make direct physical contact with it, Hatfield explained.
The problem is, tumors can hide from the attack by exploiting the system of cellular “off switches” the body uses to keep the immune system in check, a mechanism known as immune checkpoints.
Borrowing from “Star Trek,” Amiji said the tumor puts up a StarFleet-style shield that makes direct access difficult.
Keytruda, helps by blocking one of the off switches and allowing the T-cells to keep working, he explained.
Together the two treatments are “poking two different pathways,” Hatfield said. The vaccine trains T-cells to find their target, while Keytruda clears the way for the attack.
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Does it matter that the vaccine showed success in a phase 3 trial?
Before new treatments can become widely available, they have to clear several rounds.
“Phase one is safety,” Hatfield said. “They want to make sure this is going to be safe for larger trials.”
Phase two involves a small cohort and tests whether the treatment appears to work as intended and improve outcomes.
Finally comes the big test. “In phase three, they increase the number of patients,” Hatfield said.
Increasing the number of patients helps make the experiment more robust, since the more patients the vaccine has been tested on, the more confident the scientists can feel in their findings.
What else should we note about the vaccine?
The fact that the scientists couldn’t detect new tumors suggests the primed T cells may have successfully hunted down cancer cells too small to show up in the imaging that researchers use to look for tumors, Hatfield said.
Amiji is also excited about the ability to identify each patient’s unique neoantigens and rapidly build an mRNA vaccine around them.
However, this personalization comes with a practical challenge. “How can this be developed for thousands of patients in a finite amount of time?” he asked.
Moreover, the companies have yet to release detailed efficacy data from the Phase 3 trial, leaving experts uncertain just how big the benefit was.
“As scientists, we always want to look at data and make objective assessments,” Amiji explained.
He said he remains “cautiously optimistic,” noting that the key question is how much better the combination performed than Keytruda alone.
Hatfield added that the reported safety results are encouraging. While Keytruda comes with side effects such as inflammation, the vaccine didn’t cause a significant increase.
Northeastern professor Mansoor Amiji says personalized cancer vaccines could open the door to treating other cancers, but scientists will need to overcome barriers that make some tumors harder for the immune system to reach. Photo by Matthew Modoono/Northeastern University
Can other cancers be targeted this way?
“I think this is a first step,” Amiji said, adding that “there’s a huge number of opportunities here.”
Melanoma has been a go-to candidate because, as a skin cancer, it’s easy to access. However, immunotherapy could also target breast, ovarian, lung, pancreatic and brain tumors, he said.
However, there are some formidable obstacles.
Brain tumors are particularly difficult to access with immunotherapy given the barriers to delivering drugs to the brain, Amiji said. Likewise, pancreatic cancer, ovarian cancer “keep the T-cells at bay,” he added.
Making immunotherapy work against such cancers may require finding ways to help T-cells penetrate tumors, he explained.
Timing matters, too. These therapies work best if you diagnose patients early, before the disease and other treatments have taken a greater toll on the patient, Amiji said.
“One of the biggest calls to action” is to “come up with better screening tools” and other ways to identify cancers early and improve outcomes, Amiji said.
Hatfield said that Northeastern University’s department of pharmaceutical sciences is launching a new master’s degree in immunotherapy and precision medicine focused on using the immune system to develop targeted treatments.
Katya Poltorak is a science reporter at Northeastern Global News. Email her at e.poltorak@northeastern.edu.