HOW CAN GENOMICS BE USED TO HARNESS THE PATIENT’S OWN IMMUNE SYSTEM TO FIGHT CANCER?
Although most targeted therapies, such as immunotherapy, use information to identify when a particular therapy will be effective in a particular patient’s cancer, another exciting personalized therapeutic approach has demonstrated that strengthening the immune response against the specific tumor can be a highly effective therapeutic approach.
As noted above, each patient’s cancer has its own set of unique mutations that happen by chance—most of these mutations are not driving growth of the cancer, but instead are simply passengers traveling along with the driver mutations. Although these mutations are not technically causing the cancer, pieces of the mutated proteins they create (called “neoantigens”) can be recognized by the immune system and targeted for attack. By “priming” (i.e., “vaccinating”) the patient’s immune system against passenger mutations in the tumor (using protein fragments carrying these mutations), the immune response can be magnified, facilitating a stronger attack on the cancer. Recent work has demonstrated the effectiveness of using the patient’s own immune system to fight cancer. Promising research in skin cancer and other cancer types is now revealing how neoantigen therapy can further improve therapeutic outcomes for cancer patients.
Each person’s cancer has a number of unique passenger mutations. These passenger mutations can be identified through genome sequencing. It is not enough, however, to identify the mutations in the genome; the mutations must also be expressed as proteins in order to create neoantigens. Analysis of gene expression patterns can be used to measure the expression of these mutations, and allow personalized neoantigen therapy to be used to further improve cancer therapy. Once neoantigens that are expressed are identified, the patient can be vaccinated against those particular neoantigens, empowering the immune system to specifically attack the cancer cells. It is expected that this type of approach, which is highly individualized based on a person’s mutations, will be extremely effective against many types of cancer and can be used in conjunction with other therapies.
In addition to vaccination against personalized antigens present in cancer patients, another more generic vaccination approach has been described for prostate cancer. Ninety-five percent of prostate cancers express a protein called prostatic acid phosphatase (PAP). By boosting the immune response against PAP, a person’s immune response can be specifically tuned to target prostate cancer cells and not normal prostate cells. Thus, immune responses against generic antigens as well as neoantigens can be used to successfully target cancer cells. As with other forms of immunotherapy, these therapies can be used in conjunction with other types of treatments, thereby providing diverse avenues with which to fight cancer.