A vaccine targeting six KRAS gene mutations was tested in people before pancreatic cancer developed
A vaccine targeting six KRAS gene mutations was tested in people before pancreatic cancer developed
On 16 July, a Johns Hopkins University team described the first small phase I clinical trial in a Cancer Discovery article. The trial included 20 people with an inherited risk of pancreatic cancer and a suspicious imaging finding, usually a small cyst. In 18 participants, the vaccine induced T-cells that recognize altered KRAS. These cells remained detectable in the blood for up to two years. During a median follow-up of 16,5 months, none of the participants developed cancer.
People with an inherited risk of pancreatic cancer usually undergo regular imaging to detect the disease. If a cyst or another lesion begins to look dangerous, doctors may remove part of the pancreas. Early precancerous cells can be too small to appear on imaging.
The Johns Hopkins University team chose KRAS as the target because mutations in this gene drive the growth of more than 90% of these tumors. The same mutations also often occur in tumor precursor cells. The mKRAS-VAX vaccine contains fragments of the six most common KRAS variants. Vaccination teaches the immune system to recognize these fragments and seek out cells that display them on their surface.
A vaccine targeting a common tumor mutation has already been given to people after diagnosis. In the IDH1-vac trial, 33 patients with a brain tumor received it alongside surgery, radiation therapy, and chemotherapy. The participants in the new study did not yet have cancer. All had an inherited predisposition and a pancreatic abnormality that doctors would normally monitor.
The participants received three initial injections under the skin and one booster dose. In 18 of 20 participants, the vaccine induced two types of T-cells. One type was ready to attack the target immediately, while the other retained immune memory. Some of the vaccine-induced cells remained detectable in the blood for up to two years. Adverse events did not exceed grade one or two.
The researchers also examined the cysts. In the vaccinated group, cysts shrank or disappeared in 37,5% of participants, compared with 6,8% in a matched unvaccinated group. Participants were not randomly assigned to the groups, so this result cannot distinguish the effect of the vaccine from pre-existing differences between the groups.
The phase I trial assessed safety and the ability of the vaccine to induce an immune response. The authors reported that another study is recruiting participants to determine whether T-cells detected in the blood reach precancerous lesions within the pancreas. A larger comparative study will need to determine whether vaccination reduces the number of cancer cases.