mRNA Vaccines as Novel Immunotherapeutic Approaches in Gastrointestinal Cancers

Messenger RNA vaccines have moved rapidly from the infectious-disease area into oncology. They now represent an attractive therapeutic option for gastrointestinal (GI) cancers. Personalised constructs, designed to elicit tumour-specific T-cell immunity, have shown acceptable safety and clear immunogenicity in early-phase trials of colorectal and pancreatic cancers. These early signals are encouraging, but several obstacles still exist for routine clinical use: tumour heterogeneity, immune evasion, the difficulty of selecting the right target antigens, and the stability of the delivery platform itself. The possibility of a combination with immune checkpoint inhibitors is currently being explored to deepen and prolong responses, although the durability of benefit remains to be established. In this review, we outline the current landscape of mRNA vaccine development for GI malignancies, with particular attention to delivery strategies and multimodal immunotherapy. Finally, we discuss the directions most likely to help move these agents from the laboratory into everyday clinical practice.