Engineering virus-like particles for lymph-node targeted cancer immunotherapy: strategies, challenges, and future prospects.

Virus-like particles (VLPs) are emerging as effective platforms for cancer immunotherapy because of their strong immunogenicity and structural similarity to viruses. This review highlights recent advancements in engineering VLPs to target lymph-nodes (LNs) by enhancing antigen presentation and T-cell activation. The strategies used to achieve this include chemical modifications such as strain-promoted azide-alkyne cycloaddition (SPAAC), sulphur fluoride exchange (SuFEx) reactions, photoinduced crosslinking reactions, as well as genetic approaches such as SplitCore technology and the incorporation of unnatural amino acids (uAA). We discuss both active (dendritic-cell-mediated) and passive (lymphatic-drainage-based) targeting methods. Although VLP-based vaccines show promise in preclinical and clinical settings, challenges such as scalable production and immune variability must be addressed for their successful clinical translation.