Carbohydrate-Lectin Interactions Reprogram Dendritic Cells to Promote Type 1 Anti-Tumor Immunity

Area of Science:

• Immunology
• Vaccinology
• Oncology

Background:

• Cancer vaccine development requires strategies to induce tumor-specific cellular immunity.
• Dendritic cell (DC) activation via lectins and toll-like receptors (TLRs) shapes immune responses.
• Identifying receptors that drive type 1 cellular immunity is crucial for effective vaccines.

Purpose of the Study:

• To engineer a virus-like particle (VLP) vaccine capable of directing dendritic cell (DC) activation for robust type 1 cellular immunity.
• To exploit dual signaling pathways involving DC lectins and TLRs for enhanced cancer vaccine efficacy.
• To evaluate the therapeutic potential of a novel glycan-costumed VLP vaccine in a murine melanoma model.

Main Methods:

• Engineered glycan-costumed VLPs displaying a DC-SIGN-selective ligand and encapsulating TLR7 agonists.
• Delivered programmable peptide antigens to DCs for activation.
• Assessed T cell responses (CD4+, CD8+), tumor infiltration, tumor growth inhibition, and protection against tumor reintroduction in a murine melanoma model.

Main Results:

• Glycan-costumed VLPs induced robust DC activation and type 1 cellular immunity, generating tumor antigen-specific Th1 CD4+ and CD8+ T cells.
• Vaccination with tailored VLPs significantly inhibited tumor growth in a murine melanoma model.
• VLPs lacking the DC-SIGN ligand promoted humoral immunity with limited tumor control, highlighting the importance of the glycan-costumed approach.

Conclusions:

• DC lectin-driven immune reprogramming using engineered VLPs is a promising strategy for cancer vaccine development.
• The modular programmability of VLP platforms allows for tailored immune responses.
• This approach provides a framework for advancing cancer immunotherapies and vaccines by directing cellular immunity.