Immunotherapies have revolutionized the treatment of cancer, resulting in cures in subsets of cancer patients, yet remain ineffective for the majority of patients. We aim to expand the use of curative immunotherapies to all cancer patients (pediatric and adult). Our work aims to address the major bottlenecks preventing wider use of immunotherapies by applying first principles: discovering tumor-specific targets using multi-omics approaches and engineering target-specific immune receptors using combined computational and experimental techniques. We develop and employ technologies at the intersection of genomics, proteomics, immunology, antibody engineering and computational biology.  We are generating a pipeline of new therapies for cancer patients in need as well as technologies to enable personalized immunotherapies. Resulting from these approaches, our novel class of peptide-centric (PC)-CAR T cells potently eradicate tumors in preclinical models and are entering clinical trials in 2023.