The COVID-19 pandemic has caused incomprehensible suffering and loss of life in the last few years. But if there’s a silver lining in this ongoing tragedy, it may be how the rapid discovery and implementation of the highly effective COVID-19 vaccine is fueling the momentum and continued research of similar personalized Messenger RNA (mRNA) vaccines, including those for fighting cancer.
Consider the ground-breaking work of Vinod Balachandran and Benjamin Greenbaum, co-leaders of the SU2C–Lustgarten Foundation Pancreatic Cancer Convergence Research Team, whose initial research actually pre-dates the pandemic. They are now running the first clinical trial of a personalized mRNA vaccine for pancreatic cancer patients.
Ironically, the duo had seemingly little in common at first: Balachandran was a general surgery resident at New-York Presbyterian Hospital, honing his surgical skills and learning the limits of modern medicine in saving patients’ lives. Greenbaum had a graduate degree in physics and had published papers on chaos and quantum mechanics while working at Los Alamos National Laboratory.
But a fateful connection brought them together. The pair met when Greenbaum won a 2016 SU2C Sharp Award to study cancer immunotherapy with one of Balachandran’s colleagues at Memorial Sloan Kettering Cancer Center. They credit much of their fruitful collaboration to SU2C.
“Stand Up goes a long way to try to facilitate and forge these collaborations between people that span different disciplines when they can recognize there’s a common goal,” says Balachandran. “I think they did a fantastic job here recognizing that, even though we were approaching it from different angles, our missions were aligned; we both wanted to make cancer vaccines.”
The researchers teamed up in 2017 to study what distinguishes long-term survivors of pancreatic cancer – the 9 percent who live more than 5 years after diagnosis—from other patients. They discovered that, up to 12 years after recovering from cancer, survivors had specialized immune cells that recognized cancer proteins called neoantigens.
A vaccine, Balachandran and Greenbaum thought, might be able to coax the immune systems of all pancreatic cancer patients to recognize these neoantigens. The challenge: not all patients’ tumors have the same neoantigens.
“Designing a vaccine is, at some levels, more challenging in cancers than in viruses,” says Greenbaum. “Tumors are diverse between patients and have evolved to not only avoid the immune system but suppress it.”
Facing up to these challenges, the research team started designing a system in which they could customize an mRNA vaccine for pancreatic cancer patients based on the combination of neoantigens present in each patient’s tumor. Greenbaum’s analytical approach coupled with Balachandran’s immunological and clinical knowledge helped them determine the most effective way to create this kind of personalized vaccine.
In December 2019, their team launched a phase I clinical trial to test mRNA vaccines in pancreatic cancer – a full year before mRNA vaccines against COVID-19 mRNA vaccines became available.
In the two years since, both Balachandran and Greenbaum say that the promise of the clinical trial, and the intellectually rich collaborations borne of their SU2C team, helped keep them engaged in their work through the COVID-19 pandemic. In 2020, BioNTech—the same German company that was producing the pancreatic cancer vaccine in collaboration with Memorial Sloan Kettering—teamed up with Pfizer on their COVID-19 mRNA vaccine. The first results on the Pfizer-BioNTech vaccine were exciting not only for the promise of managing COVID-19, but for informing the development and safety of other mRNA vaccines, the researchers say.
“I think people have more confidence in the platform because of what’s happened with COVID,” says Greenbaum.
“It was not only exciting for us, but for our patients to see data on how effective other mRNA vaccines could be,” agrees Balachandran.