New vaccine may be potential off-the-shelf treatment for pancreatic, colorectal cancer

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A new vaccine has encouraging early results as a potential 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). The vaccine targets tumors with mutations (or changes) in the KRAS gene, which is the driving force behind many cancers..

This cancer vaccine differs from other types of pancreatic cancer vaccines in that it is custom-made for each patient using messenger RNA (mRNA). Both are therapeutic vaccines given after surgery to prevent or delay the return of cancer in high-risk patients.

“Having an ‘off-the-shelf’ vaccine would make treating patients easier, faster and less expensive,” said Eileen O’Reilly, a medical oncologist and pancreatic oncologist who helped lead the trial and is one of the corresponding authors of the published study. Nature’s medicine. “It offers hope for people with pancreatic and colorectal cancer who have been out of effective treatment after their disease came back.”

Dr. O’Reilly is a co-corresponding author Nature’s medicine Study with Shubham Pant, MD, of MD Anderson Cancer Center, and Christopher M. Hawke, MD, PhD, of Elisio Therapeutics.

Results of clinical trials for pancreatic and colorectal cancer KRAS vaccines

The phase 1 trial involved 25 patients who had specific KRAS mutations in pancreatic or colorectal cancer and were at high risk of the cancer returning after surgery. The results show that the vaccine is safe and stimulates the patient’s immune system to produce cancer-fighting cells:

  • 84% of patients had the desired immune response, meaning that immune T cells targeting KRAS-mutated cancer cells were activated and increased in number.
  • Also in 84% of patients, a marker for prolongation of cancer cells -; Amount of circulating tumor DNA in blood -; was reduced. In 24% of patients, tumor DNA was completely absent.
  • Perhaps most significantly, patients who had superior T cell responses also experienced longer periods of time without the disease returning, known as relapse-free survival.

Patients whose immune systems were shown to respond to the vaccine had delayed cancer recurrence compared to patients who did not respond to the vaccine. That’s the kind of early clinical impact we can make.”

Eileen O’Reilly, MD, medical oncologist and pancreatic cancer specialist

How do off-the-shelf vaccines targeting KRAS mutations differ from personalized mRNA vaccines?

A different approach to activating immune cells has been pioneered by surgical oncologist Vinod Balachandran, MD. Investigating personalized mRNA vaccines using proteins from a patient’s pancreatic tumor would alert their immune system that the cancer cells are foreign. In this way, the mRNA vaccine trains the body to protect itself from cancer cells. The vaccine is now being tested in phase 2 research studies at MSK and other institutions.

Personalized vaccines -; Time to commit -; There are also challenges. They are time consuming and expensive to manufacture. In contrast, an off-the-shelf vaccine produced in batches can be given to patients with minimal delay and would be cheaper to produce.

“These results are exciting because they show that we may have multiple ways to activate immune cells to target pancreatic cancer,” Dr. O’Reilly said.


Journal Reference:

pant., etc (2024). A lymph-node-targeted, MKRAS-specific amphiphile vaccine in pancreatic and colorectal cancer: the phase 1 AMPLIFY-201 trial. Nature’s medicine.

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