In an early trial, a unique vaccine for everyone was promising to prevent the difficult pancreatic cancers from being treated.
Pancreatic cancer is particular concern. The five -year survival rate is approximately 13%, and up to 80% of pancreatic cancers can return.
“If I asked me what illness I need something to prevent recurrences, this would say,” said Dr. Zev Wainberg, co -director of the University of California, Los Angeles, the Gastrointestinal Oncology program, which directed the clinical trial of phase 1.
The vaccine is directed to one of the most common genetic drivers of cancer: the mutations of the Kras gene.
KRAS mutations occur in approximately a quarter of all cancers, including up to 90% of pancreatic cancers and approximately 40% of colorectal cancers. Its ubiquity makes KRAS mutations a great goal for cancer therapies, but mutations have been considered impossible to aim with medications.
To achieve this, the vaccine uses short amino acid chains called peptides that teach immune cells to recognize and attack cells with Kras mutations.
“The critical step is to involve an immune response,” Wainberg said.
Cancer vaccines are a growth field of research, but many of these vaccines are customized for the patient. This means that your tumor must be sequenced to create a specialized vaccine. However, the vaccine in the current study does not need to be personalized and would be available outside the shelf.
Killing persistent cancer cells
In phase 1 trial, published on Monday in Nature Medicine, Wainberg and a team of doctors from all over the country recruited 20 people with pancreas cancer and five with colorectal cancer. (They also chose to include some patients with colorectal cancer because Kras mutations are also a common driver of colorectal cancers, and people whose colorectal cancer is driven by these mutations are more likely to have a recurrence, Wainberg said.
All in the essay had kras mutations and had undergone a standard treatment, generally chemotherapy and surgery, to eliminate most of their tumors.
After surgery, blood tests showed that a handful of cancer cells, called microscopic residual disease, which is very common with pancreatic cancer.
“We are talking about cancer that is so microscopic that we cannot see it in the scan,” said Dr. Scott Kopetz, professor of gastrointestinal medical oncology at the MD Anderson Cancer Cancer Cancer of the University of Texas in Houston.
These cells can travel to other parts of the body and grow in metastase tumors, which caused a fatal recurrence of cancer. Chemotherapy can kill some of these cells, but some usually remain in the body.
“Being realistic, if we want to kill even the last cancer cells and really cure people, it must involve the immune system,” said Stephanie Dougan, an associated professor of immunology and virology of cancer at the Dana-Farber cancer Institute in Boston. “We have been really bad to get an immune response in pancreas cancer.”
After surgery, all in the trial obtained up to six doses of primer of the experimental vaccine, called eli-002 2p. Thirteen also received reinforcement shots. The whole process took 6 months.
Around 85%, 21 of the 25 participants, set up an immune response to KRAS mutations, and approximately two thirds of these patients had an immune response that seemed to be robust enough to avoid persistent cancer cells.
In addition, in almost 70% of people in the trial, the vaccine seemed to trigger an immune response not only to Kras mutations, but to other tumor cells that were not in the vaccine. Some people were “super responders” who set up an abnormally strong immune response to cells.
“Those people had the best results,” Wainberg said. Currently, his equipment is running a randomized phase 2 trial to prove the durability of the vaccine and compare if the vaccine is more effective than the standard of care, which would generally be monitoring the patient for recurrence.
In phase 1 trial, people with pancreatic cancer survived for an average of 29 months and lived free of recurrence for more than 15 months after vaccination.
“That far exceeds rates with dry cancers,” Wainberg said, referring to cancers that can be eliminated with surgery.
A growing field
Cancer vaccines have been incredibly difficult to make, in part because cancer cells have many of the same proteins as healthy cells, which hinders safe objectives. Recently, medical technology has made the advances the researchers needed to improve treatment. Refined RNM technology and gene sequencing become faster and cheaper have replaced cancer vaccines in clinical trials, Dougan said.
Custom RNM cancer vaccines are promising in pancreatic and colorectal cancers, but a single -size cancer vaccine would make the treatment faster and more cheaper. The previous trials that use peptide vaccines have not been able to prevent cancer recurrences. But peptides in the new vaccine, called lipophilic peptides, have something that the past treatments did not, a tail.
“That tail adheres to lymph nodes where immune cells are activated,” Dougan said. “You need something to start the immune system, and simply inject cancer cells or dead peptides does not work so well.”
The most advanced clinical trials will have to confirm the results of the phase 1 trial, but promising results have also been observed in other cancer vaccine tests and could pave the way for important advances to prevent cancer recurrences. Memorial Sloan Kettering is also working on a standard vaccine that goes to a genetic mutation that is in 95% of people with acute myeloid leukemia. The vaccine trial data directed by KRAS published on Monday showed that it is likely to be directed to these mutations with non -customized vaccines, something that the researchers thought it was impossible.
“The fact that long -term survival really corrected with the response of T cells suggests that the vaccine caused this,” said Dougan, referring to specific immune cells activated by the vaccine. “The idea that you can point to Kras is really exciting.”
