T Cell Receptors Targeting Mutations in RNA Splicing Factors
RNA splicing is a fundamental process in eukaryotes in which messenger RNA is prepared to be translated into a protein. Missense mutations in splicing factors can result in the creation of malformed proteins and are associated with a wide array of cancers. Neoantigens arising from somatic mutations in spliceosome genes represent ideal immunologic targets for personalized cancer immunotherapy.
Description
Pitt researchers isolated genes encoding two unique T cell receptors (TCRs) capable of recognizing peptide epitopes from a mutated RNA splicing factor commonly found in uveal melanoma, chronic lymphocytic leukemia, myelodysplastic syndromes, and breast cancer. When these genes were introduced into a donor T cell, mutation reactivity was conferred without eliciting reactivity against the non-mutated form of the protein. Cancer patients with similar mutations stand to benefit greatly from personalized immunotherapy focused on genetically engineering human T cells with TCRs targeted to this mutated RNA splicing factor.Applications
· Treating cancer caused by mutated RNA splicing factorsAdvantages
· Does not affect non-mutated forms of the proteins· Applicable to a wide variety of cancers
· No other targeted cancer therapies specific for mutant RNA splicing factors