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Adoptive T Cell Therapy for Cancer using Mutant KRAS-specific T Cell Receptors for T Cell Engineering
University of Pennsylvania
Cell therapy
Oncology
Hit To Lead or Lead Optimization
• Using blood samples form healthy donors and cancer patients, the team has devised a platform to identify and isolate TCR sequences that bind to peptide-HLA class I complexes with high specificity and potency for mKRAS.
• Based on this knowledge, the team has developed a novel mKRAS cancer vaccine (currently being tested in an actively enrolling clinical trial) and has also advanced the data set needed to file an IND for mKRAS TCR-based adoptive T cell clinical trial.
• In addition, knowledge of these immunogenic peptide-HLA complexes has driven the development of novel laboratory tools useful for discovery and patient assessment, such as reporter cell lines and dextramers.
• The platform and approach is deployable for isolating TCRs specific for other mutated oncogenes, beyond KRAS.
WO2020154617A1
Biochemical and functional characterization of mutant KRAS epitopes validates this oncoprotein for immunological targeting. Nat Commun, (2021)