Improving anti-cancer T cells via alternative splicing modifications

Alternative splicing (AS) involves the selective inclusion and exclusion of exons from a nascent pre-mRNA that results in various protein sequences. Activated T cells display dynamics in isoform ratios of immune modulatory receptors and of splicing factors. Splicing variants of immune receptors may act in opposite directions but splicing factors are the major category of proteins that undergoes splicing shifts. By the use of splice-switching antisense oligonucleotides or splice-disrupting gene edits, a new avenue of transcriptional manipulations opens up to produce T cells with improved tumoricidal capacity for successful implementation of adoptive cell therapy against cancer.