Immunotherapeutic target identification
Defining the cell surface landscape (surfaceome) of diagnostic and relapsed neuroblastoma
Immunotherapy approaches hold great promise for the treatment and potential cure of childhood and adult malignancies. However, the optimal cell surface proteins to target at diagnosis and relapse remain unknown. With the support of the W.W. Smith Charitable Trust and an Innovation Award from Alex’s Lemonade Stand Foundation (ALSF), we developed an integrative multi-omic approach to identifying and validating cell surface proteins to serve as targets for immunotherapy. We are comprehensively profiling the cell surface landscape (surfaceome) of neuroblastoma at both diagnosis and relapse. To do this, we are utilizing a combination of human-derived neuroblastoma cell lines, patient derived xenograft models, and frozen tumor samples from patients. Knowledge of this repertoire of proteins (surfaceome), in combination with extensive normal tissue expression data, will greatly facilitate the identification of new and/or combinatorial immunotherapeutic targets. Our lab is further validating cell surface expression and demonstrating functional relevance of prioritized cell surface candidates. We will deliver (1) the definable landscape of cell surface protein expression (surfaceome) in neuroblastoma, including how these proteins evolve under the selective pressure of chemotherapy, and (2) a high confidence set of validated cell surface proteins to undergo subsequent antibody-based or Chimeric Antigen Receptor (CAR) T-Cell development. Recently, through a collaborative U54 within the new Pediatric Immunotherapy Discovery and Development Network (PI-DDN), we are extending our multi-omic surfaceome approach to additional high-risk childhood cancers.