A new vaccine shows promising early results as an off-the-shelf treatment for certain patients with pancreatic or colorectal cancer, according to a study co-led by researchers at Memorial Sloan Kettering Cancer Center (MSK). It is said that it shows.This vaccine targets tumors with mutations (or changes) in the KRAS gene, which is the driving force behind many cancers..
This cancer vaccine is different from other types of pancreatic cancer vaccines, which are custom-made for each patient using messenger RNA (mRNA). Both are therapeutic vaccines given after surgery to prevent or delay cancer recurrence in high-risk patients.
“An ‘off-the-shelf’ vaccine would make it easier, faster and cheaper to treat more patients,” said Eileen, a clinical oncologist and pancreatic cancer specialist. Dr. O’Reilly says. She is one of the corresponding authors of the study published in . natural medicine. “This gives hope to patients with pancreatic and colorectal cancer who have not received effective treatment even if their disease returns.”
Dr. O’Reilly is natural medicine The study was conducted with Shubham Pant, MD, of MD Anderson Cancer Center, and Christopher M. Haqq, MD, PhD, of Elicio Therapeutics.
Pancreatic and colorectal cancer KRAS vaccine clinical trial results
The phase 1 trial enrolled 25 patients with specific KRAS mutations in pancreatic or colorectal cancer who were at high risk for their cancer to return after surgery. Results demonstrated that the vaccine is safe and appears to stimulate patients’ immune systems to produce cancer-fighting cells.
-
84% of patients had a favorable immune response. This means that immune T cells targeting KRAS-mutated cancer cells were activated and their numbers increased.
-
Markers of residual cancer cells (the amount of tumor DNA circulating in the blood) also decreased in 84% of patients. Tumor DNA was completely absent in 24% of patients.
-
Perhaps most importantly, patients with higher T-cell responses also had longer periods without disease recurrence, known as relapse-free survival.
“In patients whose immune systems appeared to respond to the vaccine, their cancer returned later than in patients who did not respond to the vaccine,” Dr. O’Reilly says. “This is the type of early clinical effect we can build upon.”
Differences between off-the-shelf vaccines and personalized mRNA vaccines targeting KRAS mutations
Another approach to activating immune cells is being led by surgical oncologist Vinod Balachandran, MD. He is studying whether a personalized mRNA vaccine using proteins from a patient’s pancreatic tumor could alert the patient’s immune system that the cancer cells are foreign. In this way, mRNA vaccines train the body to protect itself from cancer cells. This vaccine is currently being tested in Phase 2 research studies at MSK and other institutions.
An “off-the-shelf” vaccine would make it easier, faster and cheaper to treat more patients.
While personalized vaccines hold promise, they also have challenges. It takes time to make and costs money. In contrast, off-the-shelf vaccines produced in batches can be administered to patients with minimal delay and are cheaper to produce.
“These findings are interesting because they indicate there may be multiple ways to activate immune cells to target pancreatic cancer,” Dr. O’Reilly says.
Targeting KRAS-G12D and KRAS-G12R mutations
Researchers have long considered KRAS mutations to be a prime target for therapy. Recently, an effective drug has emerged that blocks a specific mutation called KRAS. class-G12C, commonly seen in lung cancer.
“This was a major advance in the decades-long effort to find a good KRAS therapy,” says Dr. O’Reilly. “but class-G12C mutations are present in only 1% of pancreatic cancers. ”
The new vaccine can activate immune cells targeting different KRAS mutations called KRAS mutations. class-G12D and class-G12R, causes approximately 90% of pancreatic cancers and 40% of colon cancers. The vaccine contains synthetic peptides (short chains of amino acids) that can trigger immune cells to target cancer cells with these mutations.
How to get KRAS vaccine
The KRAS vaccine will be administered in four locations, one in each arm and leg. The peptides travel to nearby lymph nodes, which are filled with cells important for generating an effective immune response.
Patients in the trial received the vaccine in two stages. Six doses were administered in the primary phase, followed by four doses in the booster phase several months later. Although the vaccine caused mild side effects such as pain and fatigue, Dr. O’Reilly reported that it was better tolerated than standard treatments such as chemotherapy, radiation, and targeted drugs.
Good results obtained in the early stages, advancing to Phase 2 trial
To confirm these initial results, a randomized Phase 2 trial will begin in December 2023 to test patients in the U.S. who have completed treatment for pancreatic cancer, have tumors with KRAS mutations, and are at high risk of disease recurrence. More than 150 people participated at multiple facilities. Vaccines at this stage target more KRAS mutations compared to the first vaccine. Participants will be divided into two groups, with two-thirds randomly vaccinated and one-third observed.
“We hope that this next step will provide further evidence that the vaccine can generate a strong immune response that can be translated into improved clinical outcomes, particularly for pancreatic cancer.” O’Reilly says the doctor. “Many groups at MSK are collaborating on these vaccines and KRAS therapies for pancreatic cancer, and everyone is very interested in knowing which approach is best for development. It is reassuring to know that there may be multiple new treatment options for such a difficult disease.”