Alix Seif Laboratory

Led by Alix E. Seif, MD, MPH, researchers in the Seif Laboratory are focused on manipulating the human innate and immune systems to treat children with acute lymphoblastic leukemia (ALL). The long term goal of the research conducted in this laboratory is to identify innate and adaptive immune mechanisms that can be used to treat pediatric ALL more effectively, and with less toxicity, than existing therapies.

Ongoing research in the Seif Laboratory demonstrated that immunostimulatory synthetic DNA molecules (CpG ODNs) that stimulate the innate immune system can induce anti-leukemia immune responses in pediatric ALL. They also showed that CpG ODNs induce both strong innate and adaptive anti-leukemia responses in animal models of disease. The results of these studies are being used to design clinical trials to evaluate the safety and efficacy of CpG ODNs as treatments for children with relapsed ALL.

Other studies in the Seif Laboratory are directed at developing new strategies that induce durable immune-mediated protection against ALL disease progression. These studies are being conduced in a unique transgenic mouse model of ALL that was created in the Seif Laboratory. Results from these studies suggest that a multi-antigen immune response may be required for durable long-term protection against ALL disease progression. Immune tolerance to individual antigens will be an important hurdle to overcome, and studies are under way to identify strategies to circumvent tolerance.

Additional studies in the Seif Laboratory are studying the ability of certain chemotherapy drugs already in use, such as mitoxantrone and azacitidine, to induce an immunogenic type of tumor cell death to potentiate adaptive immune responses to ALL. Studies are underway to examine the effects of these drugs on antigen presentation in ALL tumor cells to determine if immunogenic tumor cell death can stimulate adaptive immune responses in pediatric ALL by disrupting immune tolerance.

Future studies in the Seif Laboratory will continue to focus on identifying novel methods to generate long-term anti-leukemic immune responses to safely and effectively treat children with ALL.