Recent Advances in Lipid Nanoparticles for Cancer Vaccines: From Antigen Delivery to Personalized Immunotherapy

In recent years, lipid nanoparticles (LNPs) have shown great promise as highly flexible delivery systems for cancer vaccines, which enable effective cargo delivery and allow for controlling their distribution, cell-targeting ability and immunogenicity. Innovations in ionizable lipid chemistry, biodegradable formulations, RNA engineering and LNP design resulted in improvements in RNA encapsulation, endosomal escape, delivery outside the liver, and targeting of lymphoid organs and antigen-presenting cells. All these achievements led to an expansion of strategies for developing cancer vaccines from using only mRNA to personal neoantigen vaccines, self-amplifying RNA (saRNA), circular RNA (circRNA), peptide/protein vaccines, and multi-purpose platforms that combine antigen delivery and modulation of the immune system. LNPs are also studied as tools for altering the tumor microenvironment (TME) and boosting anti-tumor immunity through local delivery of cytokines and innate immune modulators. Preliminary clinical results with personalized mRNA neoantigen vaccines show strong potential for this approach. However, inflammatory toxicity, suitability for repeated dosing, off-target delivery, difficulties with large-scale production, formulation stability, personalized production schedule and regulatory issues are still significant challenges. New biodegradable and PEG-free formulations, innovations in manufacturing and lyophilization technology, and AI-based approaches in lipid screening could help overcome some of these problems.