Noninvasive Transdermal Administration of mRNA Vaccines Encoding Multivalent Neoantigens Effectively Inhibits...

Area of Science:

• Oncology
• Immunology
• Biotechnology

Background:

• Developing effective tumor vaccines is hindered by challenges in obtaining specific tumor antigens.
• Multivalent antigen vaccines are considered more effective for antitumor therapy.

Purpose of the Study:

• To develop a novel multivalent mRNA vaccine (MmRV) for melanoma using mannosylated chitosan-modified ethosomes (EthsMC).
• To evaluate the efficacy of transcutaneous immunization patches (TCIPs) loaded with MmRV and/or siRNA against PD-L1 (siPDL1) in melanoma-bearing mice.

Main Methods:

• Preparation of MmRV encapsulated in EthsMC for transcutaneous immunization (TCI).
• Development of TCIPs loaded with MmRV or siPDL1.
• Application of TCIPs to melanoma-bearing mice and assessment of immune responses and tumor growth.

Main Results:

• MmRV effectively induced dendritic cell maturation, outperforming single neoantigen mRNA.
• TCIPs significantly elevated TNF-α, IFN-γ, and IL-12 levels, inhibited tumor growth, and promoted T cell infiltration.
• Combination therapy of MmRV and siPDL1 exhibited synergistic antitumor effects with good biosafety.

Conclusions:

• A noninvasive TCI system with MmRV and siPDL1 offers a promising approach for melanoma treatment.
• The combination therapy demonstrates superior efficacy compared to monotherapy.
• This novel delivery system provides a convenient and safe method for cancer immunotherapy.