For some, the low point came in May, when the White House proposed an unprecedented cut of more than 40% to funding for the National Cancer Institute. Twenty-six days later, in an apparently unrelated move, the US Department of Health and Human Services canceled a $590 million deal with Moderna to develop an mRNA-based vaccine against emerging pandemic influenza. In August, HHS followed up by announcing it would no longer fund mRNA research through the Biomedical Advanced Research and Development Authority. The latter move involved the cancellation of 22 separate contracts.
More recently, the FDA canceled its review of Moderna’s mRNA-based flu vaccine, while criticizing the design of the company’s clinical trial, but the agency reversed its decision a week later after fierce criticism.
FDA Commissioner Dr. Marty Makary has said the agency bears no animus toward mRNA and that it terminated contracts last year solely to save taxpayer money. “The companies that made mRNA vaccines made over $50 billion. They can fund their own research,” Makary said at a news conference in February.
Still, many researchers who once saw a bright future felt their faith shaken. “The external threats are real,” Wu said. “It forced us to really step back and think. I wouldn’t be genuine if I said we weren’t all concerned.”
Dr. Ryan Sullivan, director of the Center for Melanoma at Mass General Brigham Cancer Institute, says mistrust of mRNA vaccines since the pandemic has at times made it harder to recruit people into his clinical trials.
“Most people don’t have significant concerns, but some are reluctant,” Sullivan said. “The skepticism over vaccines in general is a little bit lessened around cancer vaccines, but not totally, and some people are resistant to the concept, even when they’re fighting cancer.”
One technology, many paths
Sullivan is an investigator on multiple studies with mRNA vaccines, including a large-scale trial run by drugmakers Moderna and Merck, testing an mRNA-based therapy in combination with Keytruda, an immunotherapy drug, as a treatment for melanoma. In January, the companies announced that the combination cut the death rate for participants in their study by 49% over five years. A larger phase 3 trial is underway, and the companies are also testing the therapy against non-small cell lung cancer, bladder cancer and renal cell carcinoma.
Like the vaccine that helped Blechner, Merck and Moderna’s melanoma treatment is personalized, meaning an individual patient’s tumor cells are used to engineer a highly specific immune response. Another approach involves what are called generalized or off-the-shelf vaccines, that are not tailored to each individual patient. BioNTech and the Moderna/Merck collaboration are both working on approaches that use mRNA to encode and deliver a predefined set of antigens – immune targets – that are typically shared across patients with a given tumor type in hopes of stimulating the immune system into a more aggressive response.
Dr. Elias Sayour, a pediatric oncologist and researcher at the University of Florida, has gone a step further in the “generic” direction, testing mRNA vaccines that don’t code for any specific antigen at all. In a study published last year in the journal Nature Biomedical Engineering, Sayour treated mice with a generalized vaccine, using mRNA to stimulate production of a protein called PD-L1, making their tumors more susceptible to immunotherapy. It worked.
