Grant: Travel Awards - Institute Community Support

Acute myeloid leukemia (AML) is an aggressive blood cancer with very poor survival rates. Standard treatments such as chemotherapy often fail, and many patients relapse. Bone marrow or stem cell transplants from healthy donors can sometimes cure AML by enabling the donor's immune system to attack leukemia cells. However, this approach carries significant risks: if the immune response is too weak, the leukemia returns; if it is too strong, it causes graft-versus-host disease (GvHD), where donor cells attack healthy tissues. My research focuses on a unique type of immune cell called double-negative T cells (DNTs), which can recognize and kill leukemia cells with minimal side effects. Our team has demonstrated that DNTs can be safely expanded from healthy donors and infused into patients in early clinical trials. However, in some cases, natural DNTs are not potent enough to completely eliminate AML. To address this, I am enhancing DNTs by engineering them with a chimeric antigen receptor (CAR) that enables them to recognize CD4-a molecule frequently expressed on AML cells but absent from healthy stem and progenitor cells. Notably, AML patients with lower CD4 levels tend to live longer, suggesting that targeting CD4 could not only destroy leukemia but also reshape the immune environment to prevent relapse. To ensure safety, I am also incorporating a built-in "safety switch" that can deactivate the engineered cells if adverse effects occur. By combining the natural safety of DNTs with the precision of CAR technology, this project aims to develop a next-generation, off-the-shelf cell therapy that reduces relapse and improves outcomes for AML patients in Canada and beyond.