For his work developing an individually tailored, cell-specific approach to treating cancer by combining drug treatments with immune-response therapeutics, Aleksandar Obradovic is the grand prize winner of the 2023 Michelson Philanthropies & Science Prize for Immunology. Obradovic's essay details his work harnessing the anti-tumor immune response with tailored cancer immunotherapy. These therapies and single-cell RNA-sequencing data are combined with traditional cancer drugs as informed by two algorithms his team developed, one that infers protein activity (VIPER) and another that predicts drug sensitivity (ARACNe), to identify groups of cells associated with cancer treatment resistance in different tumor types. Obradovic and his colleagues at Columbia University Irving Medical Center developed these tools to identify predictive immune characteristics of patients who respond well to treatment as compared to those who do not. Obradovic notes that immunotherapy represents a paradigm shift from traditional cancer treatment, activating anti-tumor immune responses broadly and independently of tumor growth mechanisms. Nonetheless, many patients remain non-responsive to immunotherapy, motivating his own approach. "With the high levels of missing data in single-cell RNA sequencing experiments, this is like solving a crossword puzzle. ARACNe is the dictionary that tells us which letters go with which words, and VIPER is the puzzle-solver, finding the right words even when most of the letters are missing," Obradovic explained. His greatest hope for the future of his research is to translate predicted drug combination discoveries back to the design of new clinical trials and patient care and he plans to study and integrate the immune effects of radiation therapy into his approach.
Roser Vento-Tormoia is a finalist for her essay "Decoding foreign antigen tolerance: Cell atlases of human tolerogenic milieus guide transformative immunotherapies." Her research focuses on understanding how cell-cell communication and the tissue microenvironment regulate cell identity and function in the context of immunity and development. Joshua Tan is a finalist for his essay "Searching for common ground: The conserved coronavirus fusion peptide is a target of broadly neutralizing antibodies." His research focuses on understanding the human antibody response to infectious pathogens through the study of monoclonal antibodies.
