A Phase 1 clinical trial has demonstrated promising results for a personalized mRNA vaccine in delaying the recurrence of pancreatic cancer. The study, published in Nature, evaluated the mRNA vaccine autogene cevumeran in combination with surgery, chemotherapy, and the immunotherapy drug atezolizumab in patients with pancreatic ductal adenocarcinoma.
mRNA Vaccine Shows Promise
The trial, conducted at Memorial Sloan Kettering Cancer Center, involved 16 patients with surgically resectable pancreatic cancer. Each patient received a personalized mRNA vaccine designed to target specific neoantigens present in their tumor. The vaccine aimed to stimulate the patient's immune system to recognize and attack the cancer cells, potentially preventing or delaying recurrence.
Immune Response and Recurrence-Free Survival
At a median follow-up of 3.2 years, the eight patients who developed T cell responses from the vaccine had not reached their median recurrence-free survival. In contrast, the eight patients who did not develop immune responses experienced cancer recurrence after a median of 13.4 months. This significant difference suggests that the vaccine-induced immune response may play a crucial role in delaying cancer recurrence.
Dr. Vinod Balachandran, the principal investigator of the trial and senior study author at MSK, expressed optimism about the efficacy of this treatment. "We find that with RNA vaccine technology, we can teach the immune system to recognize pancreatic cancer, and this immune response could potentially last for many years," he stated. "The ability to trigger a robust, long-lasting immune response is a requisite feature for any cancer vaccine."
Mechanism of Action
The personalized mRNA vaccines work by delivering proteins found in cancer cells (neoantigens) to train the immune system to recognize cancer cells as foreign. This approach aims to generate a strong and durable T cell response, enabling the immune system to effectively target and eliminate cancer cells. The vaccine-induced CD8+ T cells, which are crucial for fighting cancer, were found to have long lifespans, with some remaining active three years following vaccination.
Pancreatic Cancer and Unmet Needs
Pancreatic cancer remains one of the deadliest cancers, with a five-year survival rate of only about 13%. Traditional therapies like chemotherapy, radiation, and immunotherapies have limited effectiveness against pancreatic cancer, highlighting the urgent need for new therapeutic approaches. The experimental mRNA vaccine offers a potential new avenue for treating this challenging disease.
Future Directions
Encouraged by the Phase 1 trial results, the researchers are planning a larger study to further test these therapeutic cancer vaccines in patients with surgically removable pancreatic cancer. This larger trial will help confirm the effectiveness of the vaccine and identify factors that may influence its efficacy. Genentech and BioNTech, sponsors of the trial, have initiated a Phase II clinical trial to evaluate the vaccine in a larger patient group, enrolling approximately 260 patients at various sites around the world.
"For patients with pancreatic cancer, our latest results continue to support the approach of using personalized mRNA vaccines to target neoantigens in each patient’s tumor," said Balachandran. "If you can do this in pancreas cancer, theoretically you may be able to develop therapeutic vaccines for other cancer types."
