Defining the role of ALCAM in immune evasion in neuroblastoma
Mentor Name: John Maris
Neuroblastoma is a pediatric cancer of the developing sympathetic nervous system. Despite intensive, multimodal chemotherapy, only 50% of children diagnosed with high-risk neuroblastoma will survive 5 years. Monoclonal antibodies targeting the cell-surface lipid GD2 prolong survival in neuroblastoma, and clinical trials of chimeric antigen receptor (CAR)-T cells targeting the protein GPC2 further underscore the potential for developing immunotherapies to provide new avenues for improved survival. Despite these successes in development, relapse remains common with antigen downregulation serving as a critical mechanism of resistance. This lab is interested in targeting proteins that are critical for tumor survival and immune evasion, as we hypothesize these targets will be robust to downregulation. Previous work in the lab has shown that the cell adhesion molecule ALCAM promotes survival, migration, and immune evasion in neuroblastoma. This project will expand our understanding of the immune role of ALCAM in neuroblastoma by investigating its interaction with the T cell receptor CD6. We will use peripheral blood mononuclear cells from CMV-infected donors to expand CMV-targeted T cells and investigate the effects of ALCAM depletion on tumor cell killing. Additionally, we will compare these CMV-targeted T cells to CAR-T cells targeting GPC2. We hypothesize that depletion of the ALCAM protein will improve both CAR-T cell killing and antigen-specific T cell killing, and high ALCAM expression will inhibit T cell activation and proliferation.
