CAR T-cell therapy is a promising treatment that can sometimes cure children whose leukemia has returned or did not respond to standard therapies. In this approach, a patient’s own immune cells (called T cells) are modified to recognize and attack leukemia cells, then infused back into the patient.
One major challenge is that CAR T cells can become “exhausted,” meaning they gradually lose their ability to grow and kill cancer cells effectively. The St. Jude team identified a gene called DNMT3A that plays an important role in this exhaustion. In earlier clinical studies, they found that DNMT3A-related changes reduced the long-term effectiveness of CAR T cells. Importantly, they also discovered that removing or blocking DNMT3A allows CAR T cells to stay active longer, helping them persist, multiply, and better eliminate leukemia cells.
Based on these findings, they have developed a new clinical trial designed to improve CAR T-cell therapy for children with high-risk leukemia. This study will test the safety and anti-cancer activity of CAR T cells that target CD19 and CD22 leukemia markers and have DNMT3A removed (DNMT3A knockout).
The trial will be open to children, adolescents, and young adults age 21 or younger whose leukemia is CD19- and/or CD22-positive and has either returned or not responded to prior treatment. Patients will receive lymphodepleting chemotherapy followed by a single infusion of these novel CAR T cells. In addition to helping participants, this study aims to advance CAR T-cell therapy for future patients with leukemia and other serious diseases.
Projects and Grants
CAR T cells gene-edited to resist exhaustion for pediatric and young adult patients with CD19- and/or CD22-positive acute lymphoblastic leukemia
