Using alternative RNA splicing to create ready-made mRNA cancer vaccines for liver cancer

Aberrant splicing events occur at a > 59-fold higher frequency than somatic mutations in hepatocellular carcinoma.

• Aberrant splicing generates substantially more immunogenic peptides with broader patient applicability (50.94% vs 4.40% population coverage).
• A selection process identified 34 neoantigens from splicing events that are prioritized for strong immunogenicity.
• In vivo experiments showed that mRNA vaccines encoding these neoantigens led to significant tumor regression.
• Enhanced infiltration of neoantigen-reactive T cells into tumors was observed following vaccination.
• The study addresses TAP deficiency in HCC by proposing the use of TAP-independent, splicing-derived neoantigens.

Simplified