Groundbreaking cancer vaccine clinical trial moves cancer vaccines one step closer to widespread clinical use in personalized medicine
Biologists are working feverishly to win the war on cancer. Among the numerous clinical trials aimed to take advantage of new pathways opened by the U.S. Food and Drug Administration (FDA), the work of The Tisch Cancer Institute of the Mount Sinai Health System is getting noticed.
Recent research out of The Tisch Cancer Institute has provided a breakthrough in preventing cancer using personalized medicine technology. This research, presented at the American Association for Cancer Research (AACR) Annual Meeting in April, showed that this new therapy could be safely provided and well-tolerated while potentially reducing the risk of disease reoccurrence.
Mount Sinai’s innovative clinical trial used a cancer vaccine that was individualized to multiple patients who had received standard treatments for a variety of cancers. These included lung cancer, ovarian cancer, breast cancer, multiple myeloma, and head and neck cancers. Each patient treated was identified as being at a very high risk of the cancer reoccurring. However, over two years later, at least four of the 13 patients enrolled in the trial were found to be completely free from any signs of cancer.
Biologists Identifying New Targets for Cancer Vaccines
Some cancer vaccines are designed to stimulate the body’s own immune system to destroy a tumor, by injecting fragments of cancer proteins found on the tumor. News out of MIT reports that researchers there have found that vaccinating against certain proteins can help to reawaken dormant T cell populations that target those proteins, strengthening the overall immune response.
“When cells begin to turn cancerous, they start producing mutated proteins not seen in healthy cells. These cancerous proteins, also called neoantigens, can alert the body’s immune system that something has gone wrong, and T cells that recognize those neoantigens start destroying the cancerous cells.
“Eventually, these T cells experience a phenomenon known as ‘T cell exhaustion,’ which occurs when the tumor creates an immunosuppressive environment that disables the T cells, allowing the tumor to grow unchecked,” states the MIT report, published Sept. 16, 2021. A complementing article appears in the journal Cell.
Cancer Vaccine Products Advancing at a Rapid Pace
A number of vaccines are advancing through the different phases of clinical trials. In addition, in recent years, the FDA opened four designations to speed the availability of drugs, such as vaccines, that treat serious diseases such as cancer:
1. Priority review
2. Breakthrough therapy
3. Accelerated approval
4. Fast track
Recent announcements related to cancer vaccine advancements include:
Ultimovacs ASA, which recently announced a “universal cancer vaccine,” and reported in late October 2021 that it recently has gained Fast Track designation from the FDA for its UV1 cancer vaccine. According to the company, the immune stimulatory vaccine for cancer is currently being investigated in combination with checkpoint inhibitors in four phase II trials: in unresectable or metastatic melanoma, ovarian cancer, head and neck squamous cell carcinoma, and malignant pleural mesothelioma.
BioNTech, notorious for its much-discussed messenger RNA COVID-19 vaccine, announced that a first colorectal cancer patient has been treated with its individualized mRNA cancer vaccine. Since 2016, BioNTech has advanced mRNA-based cancer vaccines targeting neoantigens in collaboration with its partner Genentech, states the company.
Also on the horizon is a novel study for a cancer vaccine aimed at eventually preventing triple-negative breast cancer. This study is taking place at Cleveland Clinic and is estimated to be completed in September 2022. The Cleveland Clinic study is funded by the U.S. Department of Defense. A cohort of patients, who have completed treatment for early-stage triple-negative breast cancer within the past three years and are currently tumor-free but at high risk for recurrence, will receive three vaccinations, each two weeks apart and will be closely monitored for side effects and immune response.
Unique About Mount Sinai Cancer Vaccine Breakthrough
Cancer treatments often involve immunotherapy, which boosts the body’s immune response to cancer. These treatments, however, do not often offer patient- or cancer-specific treatments, and they focus on helping the body to fight an existing cancer rather than preventing the reoccurrence of a cancer.
“While immunotherapy has revolutionized the treatment of cancer, the vast majority of patients do not experience a significant clinical response with such treatments,” said the Mount Sinai trial co-leader Thomas Marron, MD, PhD, Assistant Director for Early Phase and Immunotherapy Trials at The Tisch Cancer Institute and Assistant Professor of Medicine at the Icahn School of Medicine. “Cancer vaccines, which typically combine tumor-specific targets that the immune system can learn to recognize and attack to prevent recurrence of cancer. The vaccine also contains an adjuvant that primes the immune system to maximize the efficacy.”
For its study, the Mount Sinai team used DNA that was specific to the patients, as well as tumor-specific DNA to identify ways to activate each patient’s immune system to recognize and destroy the specific cancer that was likely to reoccur. Researchers found that these high-risk patients experienced results that enhanced their survival beyond what was expected.
“Most of the patients in our study had well over a 50 percent chance of the cancer coming back,” said Marron. “The number one thing we were interested in was, did we successfully teach the patient’s T cells, their immune cells, what to look out for and what to kill in case there were microscopic pieces of the tumors that remained in the body? Hopefully, if the patient does have residual disease, those T cells can hunt it down and kill it.”
While this initial trial did yield promising results, the cost and complexity of the trial means that the specific methods of Mount Sinai’s research will be used to guide future developments in the field of cancer vaccines rather than be clinically used themselves.
The goal of the trial “really is about informing future novel therapies,” Marron says. “Ideally, we will be able to get to the point where we do a biopsy and send it off to a lab and receive a vaccine, but that is very difficult to do now and very expensive. As the technology improves it may become possible.”
The ultimate goal that has been furthered by Marron’s team’s research is to develop a single cancer vaccine or set of cancer vaccines that cover a wide variety of patient-specific mutations. “I’m looking forward to creating what we call ‘shared neoantigen vaccines,’” Marron explains. “This is based on our understanding that certain mutations exist in a high percentage of lung cancers, pancreatic cancers, colon cancers, and other types of cancer. If we were able to make a vaccine that covers, say, 100 different mutations, we would have a vaccine that could help a majority of cancer patients in the world.”
Cancer Vaccines One Step Closer to Widespread Clinical Use
As the first clinical trial on a cancer vaccination method that can be used against multiple types of cancer, the Mount Sinai clinical trial is truly groundbreaking research. While hospitals are not yet able to offer their cancer patients comprehensive cancer vaccines, they may be able to help patients enroll in cancer vaccine trials that are showing increasing promise.
Hospital leaders and oncologists should also be aware of how cancer vaccine technology is developing and how it will be used to treat patient-specific tumors. Precision medicine technology allows cancer vaccines to target specific genetic features of cancers. Hospitals should be prepared to provide patients with ways to understand their cancer’s unique genetic traits and what precision medicine treatments will work best for their personal situation.