A team of researchers at the National Center for Tumor Diseases have developed a promising new vaccine designed to target a specific mutated protein that is commonly found in certain types of brain cancer. The vaccine was found to trigger antitumor immune responses in mice and also thwart tumor progression, raising the possibility that it could be used to treat cancer in humans. The study has been published in Nature.
In certain types of cancer, including gliomas (a broad group of brain tumors), defining early events that precipitate tumor development are mutations within a particular gene called IDH1. In around 70% of certain types of gliomas, a mutation resulting in a single amino acid substitution in the IDH1 protein results in transformation of normal cells into cancerous cells.
Some patients naturally mount an immune response against the disease because part of this mutated protein is presented on tumor cells by a component of the immune system called MHC class II. This display acts like a red flag, triggering a response by the host. Unfortunately, however, the immune response elicited is insufficient to inhibit tumor growth.
Armed with the knowledge that this mutant protein can stimulate an immune response, the researchers set out to enhance this response by developing a tumor-specific vaccine. The aim of cancer vaccines is to boost the ability of the immune system to recognize a feature of the tumor as foreign, but unfortunately most previous efforts have been fruitless.
The IDH1 mutant protein, however, seemed a promising target given the fact that it is found within the majority of cells in the tumor and exhibits little variation. The researchers therefore developed a vaccine consisting of an artificial version of a fragment of the IDH1 protein encompassing the tumor driving mutation, identical to the region presented to the immune system by MHC class II.
The team then used this vaccination in mice whose MHC molecules had been replaced with human MHC in order to more closely mimic what might happen in a human. “After vaccinating the animals with the peptide, we were able to detect immune cells and antibodies that specifically recognized the altered IDH1 of tumor cells rather than the normal form of the enzyme in healthy cells,” lead author Theresa Schumacher said in a news-release. Furthermore, the response elicited was sufficient to stop the growth of IDH1 mutant cancer cells in the mice, but did not affect the normal IDH1 protein.
While it is still too early to tell if this vaccine will be successful in humans, the researchers are encouraged by the results and a human trial is scheduled to begin as early as next year.