(April 2010) Yale Cancer Center scientists have discovered that OCT4, a protein critical in determining the fate of certain germ-cell tumors, is commonly detected and targeted by the immune system in healthy individuals.
Their findings, published in the Proceedings of the National Academy of Sciences, could lead to the development of new vaccines and therapies to target stem cells in several cancers, by boosting this naturally occurring response.
OCT4 is a critical protein of human embryonal stem cells. The researchers first made a surprising discovery that revealed that memory T cells specific for OCT4 could be readily detected in blood from 80 percent of healthy donors. Building on prior research that showed some cancer chemotherapies activate immune responses, they then tested the presence of these lymphocytes in patients with germ cell tumors (GCT) known to express OCT4.
At diagnosis, only 35 percent of GCT patients had detectable immunity to OCT4. However, these responses were induced following chemotherapy in 83 percent of the patients. Targeting dying tumor cells to dendritic cells could readily activate these immune responses, providing a possible method to activate immunity, and a strategy for development of new therapies for patients using vaccine or cell-based approaches.
“There is a lot of interest in developing strategies to specifically target pathways engaged by stem cells at the root of cancer, and the immunogenic sequences identified here provide a target that can be readily tested in the clinic,” explained Madhav V. Dhodapkar, MD, senior author of the paper.
“The surprising capacity of the human immune system to target this critical stem cell gene also has practical implications for preventing risk for cancer with regenerative therapies involving embryonal or similar inducible pluripotency (iPS) stem cells,” said Kavita M. Dhodapkar, MD, lead author.