Developing innovative immunotherapy approaches for pediatric hematological malignancies
Hematological malignancies present unique challenges for immunotherapy-based treatments. In AML, for example, there is significant overlap in antigen expression between normal and malignant cells, and the microenvironment is incredibly effective at suppressing the immune response. Our lab is interested in defining interactions between malignant immune cells and T cells. This information will help us engineer chimeric antigen receptor (CAR) T cells with better specificity and efficacy. Additionally, we aim to discover novel antigens to bypass immune escape. Our work spans preclinical and translational domains, with the goal of improving outcomes for patients with hematological malignancies.
CAR T cell therapy is a promising immune-based treatment approach. Scientists at St. Jude are working to optimize CAR T cell therapy to better meet the needs of all cancer patients. #StJudeOn
Our laboratory is focused on developing immune cell therapies for hematological malignancies with a particular emphasis on AML and T-ALL. We have projects that address antigen discovery, tumor immune evasion, persistence and efficacy of CAR T cells, and cell-cell interaction within the tumor microenvironment. There are challenges unique to T-ALL and AML and developing innovative ways to overcome those hurdles will continue to define the driving force in our laboratory.
As tumors are exposed to CAR T cells designed for a specific antigen, they have the potential to downregulate that same target. Not only is there a need to identify novel targets that are specific to the malignant cells, but it is essential to develop bi- or multi- antigen targeting techniques. Our lab is using a multi-omics approach, leveraging information from transcriptomics, proteomics, and genomics to determine what antigens are expressed on leukemia cells that aren’t expressed on normal tissues or native T cells and lead to antigen discovery. In addition, we are exploring potential antigen combinations and configurations that would prevent tumor adaptation and immune evasion.
Leukemias, especially AML, maintain a highly immunosuppressive environment, so we need to identify ways to bypass or evade the immune response. To enhance the anti-tumor activity and persistence of CAR T cells, we are expressing different types of co-stimulatory molecules on our engineered effector cells. It will also be critical to evaluate our cells in accurate models that reflect the patient condition. As such, we are exploring the use of immunocompetent AML models.
Paulina Velasquez, MD
Assistant Member, St. Jude Faculty
Department of Bone Marrow Transplant and Cellular Therapy
MS 310, Room I4109
St. Jude Children's Research Hospital