Researchers engaged on a personalised mRNA most cancers vaccine for pancreatic ductal adenocarcinoma (PDAC), a lethal type of pancreatic most cancers, used gene sequencing from tumor samples of 19 sufferers to create custom-made mRNA vaccines, concentrating on as much as 20 neoantigens. The analysis indicated that in half the sufferers, the vaccine triggered the activation of T cells that acknowledged their particular pancreatic most cancers. Post-treatment, most cancers recurrence was not noticed in sufferers with a robust T cell response to the vaccine, even after a yr and a half.
An NIH-funded group from Memorial Sloan Kettering Cancer Center has developed a personalised mRNA most cancers vaccine for pancreatic ductal adenocarcinoma (PDAC), in collaboration with BioNTech. The experimental remedy, aimed toward triggering T cell activation to battle the precise most cancers, confirmed promising leads to stopping most cancers recurrence amongst sufferers with a robust immune response, paving the way in which for a bigger scientific trial.
- A personalised mRNA vaccine in opposition to pancreatic most cancers created a robust anti-tumor immune response in half the individuals in a small examine.
- The vaccine will quickly be examined in a bigger scientific trial. The strategy may have potential for treating different lethal most cancers varieties.
Pancreatic ductal adenocarcinoma (PDAC), the commonest sort of pancreatic most cancers, is without doubt one of the deadliest most cancers varieties. Despite fashionable therapies, solely about 12% of individuals identified with this most cancers might be alive 5 years after remedy.
Immunotherapies—medication that assist the physique’s immune system assault tumors—have revolutionized the remedy of many tumor varieties. But thus far, they’ve confirmed ineffective in PDAC. Whether pancreatic most cancers cells produce neoantigens—proteins that may be successfully focused by the immune system—hasn’t been clear.
An NIH-funded analysis group led by Dr. Vinod Balachandran from Memorial Sloan Kettering Cancer Center (MSKCC) have been growing a personalised mRNA cancer-treatment vaccine strategy. It is designed to assist immune cells acknowledge particular neoantigens on sufferers’ pancreatic most cancers cells. Results from a small scientific trial of their experimental remedy had been revealed on May 10, 2023, in Nature.
After surgical procedure to take away PDAC, the group despatched tumor samples from 19 individuals to companions at BioNTech, the corporate that produced one of many COVID-19 mRNA vaccines. BioNTech performed gene sequencing on the tumors to find proteins that might trigger an immune response. They then used that information to create a personalized mRNA vaccine for each patient. Each vaccine targeted up to 20 neoantigens.
Customized vaccines were successfully created for 18 of the 19 study participants. The process, from surgery to delivery of the first dose of the vaccine, took an average of about nine weeks.
All patients received a drug called atezolizumab before vaccination. This drug, called an immune checkpoint inhibitor, prevents cancer cells from suppressing the immune system. The vaccine was then given in nine doses over several months. After the first eight doses, study participants also started standard chemotherapy drugs for PDAC, followed by a ninth booster dose.
Sixteen volunteers stayed healthy enough to receive at least some of the vaccine doses. In half these patients, the vaccines activated powerful immune cells, called T cells, that could recognize the pancreatic cancer specific to the patient. To track the T cells made after vaccination, the research team developed a novel computational strategy with the lab of Dr. Benjamin Greenbaum at MSKCC. Their analysis showed that T cells that recognized the neoantigens were not found in the blood before vaccination. Among the eight patients with strong immune responses, half had T cells target more than one vaccine neoantigen.
By a year and a half after treatment, the cancer had not returned in any of the people who had a strong T cell response to the vaccine. In contrast, among those whose immune systems didn’t respond to the vaccine, the cancer recurred within an average of just over a year. In one patient with a strong response, T cells produced by the vaccine even appeared to eliminate a small tumor that had spread to the liver. These results suggest that the T cells activated by the vaccines kept the pancreatic cancers in check.
“It’s exciting to see that a personalized vaccine could enlist the immune system to fight pancreatic cancer—which urgently needs better treatments,” Balachandran says. “It’s also motivating as we may be able to use such personalized vaccines to treat other deadly cancers.”
More work is needed to understand why half the people did not have a strong immune response to their personalized vaccines. The researchers are currently planning to launch a larger clinical trial of the vaccine.
Reference: “Personalized RNA neoantigen vaccines stimulate T cells in pancreatic cancer” by Luis A. Rojas, Zachary Sethna, Kevin C. Soares, Cristina Olcese, Nan Pang, Erin Patterson, Jayon Lihm, Nicholas Ceglia, Pablo Guasp, Alexander Chu, Rebecca Yu, Adrienne Kaya Chandra, Theresa Waters, Jennifer Ruan, Masataka Amisaki, Abderezak Zebboudj, Zagaa Odgerel, George Payne, Evelyna Derhovanessian, Felicitas Müller, Ina Rhee, Mahesh Yadav, Anton Dobrin, Michel Sadelain, Marta Łuksza, Noah Cohen, Laura Tang, Olca Basturk, Mithat Gönen, Seth Katz, Richard Kinh Do, Andrew S. Epstein, Parisa Momtaz, Wungki Park, Ryan Sugarman, Anna M. Varghese, Elizabeth Won, Avni Desai, Alice C. Wei, Michael I. D’Angelica, T. Peter Kingham, Ira Mellman, Taha Merghoub, Jedd D. Wolchok, Ugur Sahin, Özlem Türeci, Benjamin D. Greenbaum, William R. Jarnagin, Jeffrey Drebin, Eileen M. O’Reilly and Vinod P. Balachandran, 10 May 2023, Nature.
DOI: 10.1038/s41586-023-06063-y
