Their findings, published in the Proceedings of the National Academy of Sciences on April 19, 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% 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% of GCT patients had detectable immunity to OCT4. However, these responses were induced following chemotherapy in 83% 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, Arthur H. and Isabel Bunker Professor of Hematology at Yale School of Medicine and senior author on 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,” explained Kavita M. Dhodapkar, MD, Assistant Professor of Pediatrics at Yale and lead author on the paper.
Co-authors on the study include: Soroosh Radfar and Roxana Pickering from Yale University; Darren Feldman and Stefan Turkula from Memorial Sloan-Kettering Cancer Center; and Henry Zebroski and Phillip Matthews from The Rockefeller University. Funding was provided by the Dana Foundation and the National Institutes of Health.
PNAS. 2010 Apr 19.
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