Glycan-costumed virus-like particles promote type 1 anti-tumor immunity.

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

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

Afiliação

Lensch V; Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.
Gabba A; Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.
Hincapie R; School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA, USA.
Bhagchandani SH; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
Basak A; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
Alam MM; Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.
Irvine DJ; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
Shalek AK; Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Johnson JA; Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Finn MG; Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.
Kiessling LL; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.

bioRxiv ; 2024 Jan 18.

Article em En | MEDLINE | ID: mdl-38293025

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) shapes immunity by directing T cell function. Strategies to activate specific DC signaling pathways via targeted receptor engagement are crucial to unlocking type 1 cellular immunity. Here, we engineered a glycan-costumed virus-like particle (VLP) vaccine that delivers programmable peptide antigens to induce tumor-specific cellular immunity in vivo. VLPs encapsulating TLR7 agonists and decorated with a selective mannose-derived ligand for the lectin DC-SIGN induced robust DC activation and type 1 cellular immunity, whereas VLPs lacking this key DC-SIGN ligand failed to promote DC-mediated immunity. Vaccination with glycan-costumed VLPs generated tumor antigen-specific Th1 CD4+ and CD8+ T cells that infiltrated solid tumors, inhibiting tumor growth in a murine melanoma model. Thus, VLPs employing lectin-driven immune reprogramming provide a framework for advancing cancer immunotherapies.

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Texto completo: 1 Bases de dados: MEDLINE Idioma: En Revista: BioRxiv Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos