Johns Hopkins: KRAS vaccine produced immune responses in 90% of 20 people at pancreatic cancer risk

Researchers at the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center have summarized the state of therapeutic cancer vaccines, news-medical.net reports. The center was among the sites of a multicenter phase III trial of a personalized melanoma vaccine. The trial results were published in the New England Journal of Medicine, and an accompanying editorial by Mark Yarchoan appeared on Nov. 11. news-medical.netnews-medical.netnews-medical.netOpen source ↗ According to the material, the trial shows that the approach can improve outcomes for patients.

From GVAX to checkpoint inhibitors

In the late 1980s, Elizabeth Jaffee and other Johns Hopkins immunologists helped pioneer therapeutic cancer vaccines. Jaffee and Daniel Laheru brought the approach into early trials for pancreatic cancer with the GVAX vaccine, which uses genetically modified tumor cells to stimulate an immune response. Later studies showed that vaccination could generate organized clusters of immune cells within pancreatic tumors.

Work by Drew Pardoll, Suzanne Topalian and Julie Brahmer helped advance PD-1 checkpoint inhibitors, drugs that release the brakes on the immune system and are now being combined with cancer vaccines. Bert Vogelstein and Kenneth Kinzler helped show the importance of genetic mutations in determining which cancers respond to immunotherapy. Dung Le and Luis Diaz linked defects in DNA mismatch repair to responses to PD-1 blockade. Later research showed that PD-1 therapy can expand T cells that recognize neoantigens, proteins created by mutations found in cancer cells but not in healthy tissue.

This is the basis of today's personalized vaccines: identify the distinctive mutations in a patient's tumor, vaccinate against them to stimulate cancer-specific T cells, and use checkpoint blockade to keep those cells active. news-medical.netnews-medical.netnews-medical.netOpen source ↗

KRAS vaccine and liver cancer studies

Jaffee and Neeha Zaidi are leading clinical studies of an experimental vaccine targeting mutations in KRAS, a gene altered in more than 90% of pancreatic cancers. KRAS mutations can occur a decade or more before pancreatic cancer develops.

In a recent study of 20 people at elevated risk for pancreatic cancer, the vaccine was safe and generated significant immune responses in 90% of participants. Cancer-fighting immune cells were detectable for up to two years. None of the participants developed pancreatic cancer during follow-up, but larger studies with longer follow-up are needed to determine whether the vaccine can prevent the disease.

Other studies are testing whether the vaccine can stop certain pancreatic cysts from progressing to cancer, and whether combining it with other immunotherapies can help patients who already have pancreatic cancer. news-medical.netnews-medical.netnews-medical.netOpen source ↗

In a 2024 study led by Yarchoan, a personalized vaccine combined with pembrolizumab showed encouraging activity in hepatocellular carcinoma. A separate trial by Yarchoan and Marina Baretti showed responses in fibrolamellar carcinoma, a rare liver cancer. Yarchoan says that realizing the potential of cancer vaccines will require ambitious clinical trials and sustained research investment.