When they were vaccinated, the immune system’s reactivity against tumors did become elevated, the researchers reported. And as a result, their risk of developing new metastatic lesions was significantly reduced. Moderna’s cancer mRNA vaccine, which takes a different approach, similarly induced an immune response in solid tumors — work that also began years ago. And when they combined it with a checkpoint inhibitor, the therapy shrank tumors in six out of 20 patients.
Will her work bear fruit for cancer vaccines? Unlike the Moderna Biontech Covid vaccine, a cancer vaccine does not prevent cancer. Cancer vaccines will be used to treat otherwise untreatable cancers or as an adjunctive treatment.
There’s a key difference between how a vaccine would be used to treat cancers versus a vaccine that’s used for an infectious disease like COVID-19.
First, the mRNA vaccines for COVID-19 protect people from the virus. They’re prophylactic. But a cancer mRNA vaccine is an intervention (a treatment) given to patients with the hope that their immune systems would be activated in a way that would attack tumor cells.
Through their research, Pardi and others, including researchers whose work led to the development of the BioNTech and Moderna vaccines, Drew Weissman, MD, PhD, a professor of Infectious Diseases in the Perelman School of Medicine, and Katalin Karikó, PhD, an adjunct associate professor at Penn and a senior vice president at BioNTech, found that mRNA vaccines can not only prompt strong antibody responses to fight off invaders, like COVID-19, but also potent cytotoxic T cell responses.
That’s important because these T cells can kill cancer cells. They just need to be altered or motivated to do it. Think immunotherapy, like checkpoint inhibitors or chimeric antigen receptor (CAR) T cell therapy that engineers a patient’s own T cells to find and destroy cancer cells.
“A successful therapeutic cancer vaccine should induce strong T cell responses, particularly with CD8+ T cells, which have a known capacity to kill malignant cells,” said Pardi, who is currently leading studies to better understand mRNA vaccines to treat cancers, along with other diseases. Pardi was also a postdoctoral researcher in Weissman’s lab and a frequent collaborator with him and Karikó. “Therapeutic cancer vaccines would be given to cancer patients with the hope that those vaccine-induced cytotoxic T cells would clear tumor cells.”
One example is an mRNA vaccine that targets proteins called neoantigens on a tumor to fight it. A neoantigen is a new protein that forms on cancer cells when certain mutations occur in tumor DNA.
“It’s a promising group of cancer antigens to keep exploring,” Pardi said.
This brings us to "Precision Medicine"
According to the Precision Medicine Initiative, precision medicine is "an emerging approach for disease treatment and prevention that takes into account individual variability in genes, environment, and lifestyle for each person." This approach will allow doctors and researchers to predict more accurately which treatment and prevention strategies for a particular disease will work in which groups of people. It is in contrast to a one-size-fits-all approach, in which disease treatment and prevention strategies are developed for the average person, with less consideration for the differences between individuals.
Getting Personal
The biggest challenge in developing these types of mRNA vaccines for cancer, though, is just how personal it has to be. The majority of everyone’s tumor neoantigens are specific to them.
It can’t be a catch-all approach like other vaccines — it needs to be personalized, much like CAR T cell therapy, which requires taking a patient’s own T cells, engineering them to seek out a specific antigen on a tumor cell, and then infusing them back in to find and kill them.
“That’s why we need a vaccine technology that is flexible and potent, such as the mRNA technology used for COVID-19,” Pardi said. “It could be developed to give us personalized neoantigen vaccines.”
A similar vaccine for metastatic prostate cancer known as sipuleucel-T (Provenge) stimulates an immune response to prostatic acid phosphatase, or PAP, an antigen present on most prostate cancers. While it’s not mRNA technology, it is customized for each patient and been shown in clinical trials to increase the survival of men with hormone refractory metastatic prostate cancer by about four months.
So far, it’s the only one approved by the U.S. Food and Drug Administration.