2. Academic Validation
  3. Carbohydrate-Lectin Interactions Reprogram Dendritic Cells to Promote Type 1 Anti-Tumor Immunity

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

  • ACS Nano. 2024 Oct 1;18(39):26770-26783. doi: 10.1021/acsnano.4c07360.
Valerie Lensch 1,  Adele Gabba 1,  Robert Hincapie 2,  Sachin H Bhagchandani 3 4,  Ankit Basak 1 5 6 7,  Mohammad Murshid Alam 1,  Jeffery Noble 2,  Darrell J Irvine 4 8 5 9,  Alex K Shalek 1 4 5 6 7,  Jeremiah A Johnson 1 4 7,  M G Finn 2 10,  Laura L Kiessling 1 4 5 7
Affiliations

Affiliations

  • 1 Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.
  • 2 School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, Georgia 30332, United States.
  • 3 Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.
  • 4 Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.
  • 5 Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts 02139, United States.
  • 6 Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.
  • 7 Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, United States.
  • 8 Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.
  • 9 Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, United States.
  • 10 School of Biological Sciences, Georgia Institute of Technology, Atlanta, Georgia 30332, United States.
PMID: 39283240 DOI: 10.1021/acsnano.4c07360
Abstract

Cancer vaccine development is inhibited by a lack of strategies for directing dendritic cell (DC) induction of effective tumor-specific cellular immunity. Pathogen engagement of DC lectins and toll-like receptors (TLRs) is thought to shape immunity by directing T cell function. Controlling downstream responses, however, remains a major challenge. A critical goal in advancing vaccine development involves the identification of receptors that drive type 1 cellular immunity. The immune system monitors cells for aberrant glycosylation (a sign of a foreign entity), but potent activation occurs when a second signal, such as single-stranded RNA or lipopolysaccharide, is present to activate TLR signaling. To exploit dual signaling, we engineered a glycan-costumed virus-like particle (VLP) vaccine that displays a DC-SIGN-selective aryl mannose ligand and encapsulates TLR7 agonists. These VLPs deliver programmable peptide antigens to induce robust DC activation and type 1 cellular immunity. In contrast, VLPs lacking this critical DC-SIGN ligand promoted DC-mediated humoral immunity, offering limited tumor control. Vaccination with glycan-costumed VLPs generated tumor antigen-specific Th1 CD4+ and CD8+ T cells that infiltrated solid tumors, significantly inhibiting tumor growth in a murine melanoma model. The tailored VLPs also afforded protection against the reintroduction of tumor cells. Thus, DC lectin-driven immune reprogramming, combined with the modular programmability of VLP platforms, provides a promising framework for directing cellular immunity to advance Cancer immunotherapies and vaccines.

Keywords

antitumor; dendritic cell; immunotherapy; lectin; toll-like receptor; virus-like particles.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-175421
    Aryl mannoside ligand