DataVXACS NanoPaper
journal article·2024-10-01Open access

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

Valerie Lensch, Adele Gabba, Robert Hincapie, Sachin H. Bhagchandani, Ankit Basak, Mohammad Murshid Alam, Jeffery Noble, Darrell J. Irvine, Alex K. Shalek, Jeremiah A. Johnson, M. G. Finn, Laura L. Kiessling

ACS Nano· Volume 18· Issue 39
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Source abstract

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.
Source: openalex_inverted_index · Quality: baseline

Research context

OpenAlex topics: Immunotherapy and Immune Responses · Glycosylation and Glycoproteins Research · Immune Response and Inflammation

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States

School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, Georgia 30332, United States

Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States

Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States

Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts 02139, United States

Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States

Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, United States

Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States

Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, United States

School of Biological Sciences, Georgia Institute of Technology, Atlanta, Georgia 30332, United States

Funding

National Science Foundation Graduate Research Fellowship Program · Center for Strategic Scientific Initiatives, National Cancer Institute · Centers for Disease Control and Prevention · National Institute of Allergy and Infectious Diseases · HORIZON EUROPE Marie Sklodowska-Curie Actions

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