Researchers at the University of North Carolina Linebarger Cancer Center believe a rare, inherited autoimmune disease may hold the key to a promising new melanoma treatment, according to a report published in The Journal of Clinical Investigation.
Conditions where antibodies and immune cells (also known as T-cells) fight the body’s own cells are known as autoimmune diseases. Autoimmune Polyendocrinopathy Type 1 is a recessive genetic autoimmune disease that sometimes leads to vitiligo, a condition where color-producing cells in the skin known as melanocytes are attacked, resulting in blotches of colorless skin all over the body. Since melanoma derives from melanocytes, study team members suspected the same cells that attack the melanocytes could be reprogramed to fight deadly melanoma.
T-cells are a type of white blood cells that help the body fight infections. While T-cells are very good at combating viruses and other infections, to prevent autoimmunity, the cells are programmed not to attack themselves or normal cells in the body.
Most individuals have an Autoimmune Regulator (Aire) gene that destroys T-cells that threaten to attack the body’s own cells, but individuals with a missing or mutated Aire gene (such as those found in Autoimmune Polyendocrinopathy Type 1) can’t destroy the self-reactive T-cells. This mutation increases the risk of auto-immune diseases, but could also aid the body in fighting cancer.
Using ipilimumab, an FDA-approved immunotherapy that encourages T-cells to attack tumors, along with an anti-RANKL antibody designed to block Aire and protect the self-reactive T-cells that target melanoma, researchers were able to prolong survival in mice. A human study of individuals with metastatic melanoma also revealed that patients with an Aire gene mutation who were treated with ipilimumab were more likely to enjoy a progression-free survival.
Another clinical trial is planned to look at ways immunotherapy drugs can be used in combination with RANKL inhibitors to make melanoma treatments safer and more effective.
Immunotherapy enables the body’s own immune system to recognize and target cancer cells and is an exciting and promising approach to managing difficult to treat cancers. Research such as this continues to reveal new information and encouraging findings for hard-to-treat malignancies.