PLGA-PEI nanoparticle covered with poly(I:C) for personalised cancer immunotherapy

Area of Science:

• Oncology
• Immunology
• Biotechnology

Background:

• Melanoma is a deadly skin cancer with increasing incidence.
• Advanced melanoma treatments, including immunotherapy, have limitations in effectiveness.
• Novel therapeutic strategies are needed for melanoma patients.

Purpose of the Study:

• To develop a personalized neoantigen peptide-based cancer vaccine for melanoma.
• To encapsulate neoantigens within poly(lactic-co-glycolic acid) nanoparticles functionalized with polyethylenimine and coated with polyinosinic:polycytidylic acid.
• To evaluate the vaccine's immunogenicity and efficacy in stimulating anti-melanoma immune responses.

Main Methods:

• Synthesized poly(lactic-co-glycolic acid) nanoparticles (NPs) encapsulating patient-derived melanoma neoantigens.
• Functionalized NPs with polyethylenimine (PEI) and coated with the immunoadjuvant polyinosinic:polycytidylic acid (poly(I:C)).
• Assessed NP modification, neoantigen encapsulation, and stimulation of dendritic cells (DCs) and lymphocytes.

Main Results:

• Successfully modified PLGA NPs to encapsulate neoantigens and coat with poly(I:C).
• Demonstrated effective stimulation of both dendritic cells and lymphocytes by the developed vaccine.
• Observed a superior immune activation profile compared to NPs lacking poly(I:C) or antigen.

Conclusions:

• The developed nanoparticle-based vaccine effectively matures DCs for antigen presentation and enhances lymphocyte cytotoxic activity.
• The vaccine elicits an optimal and specific immune response for melanoma tumor cell elimination.
• This personalized neoantigen peptide vaccine represents a promising immunotherapy strategy for melanoma.