Enhancing the potency of 5T4 mRNA vaccine by CD70 mRNA-LNPs through ADCC and T cell boosting in prostate cancer therapy.

Abstract

Background: Prostate cancer remains a significant health challenge, as conventional treatments often fail to provide long-term benefits in the advanced stages. This study explored the potential of mRNA vaccines as novel therapeutic strategies, specifically focusing on the combination of 5T4 and CD70 mRNA delivered via lipid nanoparticles (LNPs). 5T4, which is highly expressed in various tumors but minimally expressed in normal tissues, is an ideal target for immunotherapy. CD70 was selected for its capacity to enhance T cell activation and augment the overall immune response.

Results: Our findings demonstrated that the combination of 5T4 and CD70 mRNA-LNPs significantly enhanced both humoral and cellular immunity, resulting in improved tumor suppression and prolonged survival in a prostate cancer mouse model. Mechanistically, these LNPs increased the immune responses, including elevated 5T4-specific antibodies, enhanced CD8⁺ T cell activity, and more active natural killer (NK) cells.

Conclusions: These results suggest that this combined mRNA vaccine strategy may offer more effective and durable treatments for prostate cancer and that CD70 mRNA, as an immune activator, has broader potential for cancer immunotherapy.