In the clinic, a novel cancer vaccine that is tailored to genetic mutations in a patient’s tumor shows promise. A study of 150 patients with melanoma (a type of skin tumor) who underwent surgery showed that those who received a personalized cancer vaccine in conjunction with an immunotherapy drug had a higher chance of remaining cancer-free 18 months after the operation than those who didn’t receive it.
The results reported today at the American Association for Cancer Research’s annual meeting offer the first evidence that a cancer vaccine targeting mutations in a tumor can stop its regrowth. This would be a major milestone in the field of cancer vaccines, which has been struggling for years to produce results. This could add to the growing arsenal of immunotherapies that use the immune system against cancer. Patrick Ott, a researcher at the Dana-Farber Cancer Institute who is working on similar vaccines, says, “I was very, very excited to see these results.” The new study, although small, is “a very exciting step,” according to Nina Bhardwaj from the Icahn school of medicine at Mount Sinai.
Cancer vaccines are designed to train the T-cells of the immune system to attack tumors by exposing them a protein or antigen that is released from cancer cells. Most vaccines haven’t been effective because antigens that are found on cancer cells also occur on normal cells.
As DNA sequencing costs fell in the early 2010s some scientists began to sequence the mutations found on a tumor’s cells. They then created a vaccine that delivered a few of these mutated proteins known as neoantigens which are only present on tumor cells. Ott’s group and others published several small trials since 2015 that showed neoantigen vaccinations could stimulate vaccine-specific cells in patients with solid tumours, such as melanoma and other cancers of the colon, lung and brain.
Merck and Moderna performed a randomized study for patients with advanced melanoma, which had spread to the lymph nodes, and in some cases, other sites but had been surgically removed. All patients received a drug called a checkpoint inhibitor, which blocks a protein that allows tumors to avoid T cells. The other two-thirds received vaccine infusions about every three weeks over a period of four months. The cancer vaccine was similar to Moderna’s COVID-19, which delivered messenger RNA wrapped in lipid-nanoparticles to cells. This instructed them to produce a protein – in this case up to 34 tumor-neoantigens for each patient.
The companies reported in December 2022 that the patients who received the vaccine had a 44% lower risk of dying or having a cancer recurrence. Academic collaborators presented additional details at the AACR conference: Eighty four of the 107 patients, or 79% of them, were still in remission 18 months later, compared to only 31 of fifty (62%) of those who received the checkpoint inhibitor. Jeffrey Weber, principal investigator at NYU Langone’s Perlmutter cancer Center, said that the data showed a very positive signal.
The fact that the vaccine was effective regardless of whether the melanoma tumour had many mutations is also encouraging. This suggests it may work with cancer types which have fewer mutations. These cancers are more resistant to immunotherapy because they have less differentiation from normal cells. In a larger study that will begin later this year, the goal is to confirm these findings and determine whether or not the vaccine prolongs patient’s lives. This could be a measure to encourage regulators approve it. According to immunotherapy researcher Suzanne Topalian at Johns Hopkins University, these are “intriguing early findings”. She, like other researchers, hopes to get more information, such as evidence that the patients who responded well had T cells that were specific to the neoantigens, and not just a boost in immunity from the nanoparticles of the vaccine. Weber said that the data would be published in papers submitted to journals by Weber’s team.
Other companies are testing neoantigens in randomised trials. BioNTech, Genentech and others expect to announce early results for a neoantigen-mRNA vaccine this year. This is for metastatic melanoma which cannot be removed surgically. The challenge here is that the patients’ immune systems are weakened. Gritstone Bio is also testing a neoantigen-mRNA vaccine for metastatic colon carcinoma. To boost the immune response it is combined with modified viruses carrying the neoantigens. Gritstone reported in Nature Medicine that this led to “very significant number of T cells” in several cancer patients. According to Bhardwaj. This is a promising indication of efficacy.
One of the most interesting studies to date tested a BioNTech/Genentech neoantigen pancreatic cancer vaccine. Researchers reported last year that eight out of 16 patients had T-cell responses to the vaccine, and they were still cancer free up to 2.5 years after treatment. Eight of the 16 patients did not have an immune response, and six had relapsed within 18 months. This year, the companies plan to conduct a randomized study of this vaccine against pancreatic cancer.
Vinod BALACHANDRAN, principal investigator of the trial at Memorial Sloan Kettering Cancer Center says that because pancreatic cancer has few mutations you might think it is “the last tumor type” for which a neoantigen vaccination would be effective. He will give full details in a forthcoming paper and at AACR. If you can do this with pancreatic cancer then it is encouraging to test personalized vaccines for other cancers.