A form of cancer immunotherapy termed adoptive T cell transfer (ACT) can induce long-lasting remissions in patients with advanced blood cancers. In this approach, T white blood cells specific for proteins found on the surface of cancer cells (antigens) are activated and expanded outside the immunosuppressive environment of a cancer patient's body before re-infusion as a therapy. Thus far, this promising form of cancer immunotherapy has failed to work in most patients with cancers arising from solid organs, the leading cause of cancer-related deaths in adults. Two critical gaps in knowledge limit the ability of ACT to be successfully applied to solid cancers: 1) understanding which antigens on the surface of cancer cells can be targeted by T cells that do not have the potential to cross-react and injure normal tissues, and 2) insight into what factor(s) limit the ability of transferred T cells to expand and persist following re-infusion into a patient. Dr. Klebanoff seeks to use a genetic engineering approach to simultaneously address both these issues. Success of these efforts would be a decisive step forward toward extending the ability of ACT to deliver potentially curative responses in patients with common cancers, including those arising from the breast, uterus, cervix and colon.