Perelman School of Medicine at the University of Pennsylvania
Project Term: July 1, 2022 - June 30, 2025
Advances in multiple myeloma (MM) therapy have improved survival, but serial cycles of response and relapse still lead to treatment-refractory and fatal disease in nearly all patients. To specifically target mechanisms of MM relapse, we propose to develop an immunotherapy targeting Sox2, a stem-cell transcription factor implicated in clonogenic MM growth that enables relapse.
Modern multiple myeloma therapy is initially effective in nearly all patients, but unfortunately nearly all patients eventually relapse. New medications developed over the last 20 years have steadily improved survival, but no therapy has yet been able to break the cycle of serial relapses that eventually leads to treatment resistance and fatal myeloma complications. Our objective is to develop a new myeloma treatment approach that specifically prevents regrowth of multiple myeloma in patients who have responded to standard multiple myeloma therapies.
Our strategy is to target Sox2, a protein that is thought to help multiple myeloma cells regrow after therapy. Immune responses against Sox2 might help restrain multiple myeloma in a dormant state and prevent regrowth. In this study, we are developing immunotherapy that induces immune responses against Sox2 in MM patients. We will analyze patients who are long-term responders to MM immunotherapy to see whether they develop anti-Sox2 immune responses. In patients with anti-Sox2 immune responses, we will study the T cells in these patients that recognize Sox2 and identify the receptors on these T cells that enable them to recognize Sox2. We will then undertake studies that will enable us to engineer patients’ T cells to recognize Sox2 as an immunotherapy. Our goal for this project is to complete necessary studies to initiate a clinical trial in which patients’ T cells are engineered to target Sox2. This therapy could be given to patients who have responded to prior MM therapy to prevent relapse.