Researchers working on a personalized mRNA cancer vaccine against pancreatic ductal adenocarcinoma (PDAC), a deadly pancreatic cancer, have used gene sequencing from tumor samples of 19 patients to identify up to 20 Created customized mRNA vaccines targeting neoantigens. The study showed that in half of the patients, the vaccine caused activation of patient-specific pancreatic cancer-recognizing T cells. No cancer recurrence was observed 18 months after treatment in patients with strong T-cell responses to the vaccine.
An NIH-funded team at Memorial Sloan Kettering Cancer Center collaborated with BioNTech to develop a personalized mRNA cancer vaccine for pancreatic ductal adenocarcinoma (PDAC). This experimental treatment, which aims to trigger activation of T cells to fight certain cancers, has shown promising results in preventing cancer recurrence in patients with strong immune responses and is undergoing extensive clinical trials. paved the way for
- In a small study, a personalized mRNA vaccine against pancreatic cancer elicited a strong anti-tumor immune response in half of the participants.
- The vaccine will soon be tested in large clinical trials. This approach may also treat other deadly cancer types.
Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer and one of the deadliest cancers. Despite current treatments, only about 12% of people diagnosed with this cancer survive five years after treatment.
Immunotherapy (drugs that help the body’s immune system attack tumors) has revolutionized the treatment of many types of tumors. However, to date, they have proven ineffective in PDAC. It is not clear whether pancreatic cancer cells produce neoantigens (proteins that are effective targets of the immune system).
An NIH-funded research team led by Dr. Vinod Balachandran of Memorial Sloan Kettering Cancer Center (MSKCC) is developing a personalized mRNA cancer treatment vaccine approach. It is designed to allow immune cells to recognize specific neoantigens on the patient’s pancreatic cancer cells. The results of a small clinical trial of their experimental treatment will be announced on May 10, 2023. Nature.
After surgery to remove the PDAC, the research team sent tumor samples from 19 individuals to a partner at BioNTech, which manufactured one of them.[{” attribute=””>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