Co-delivery of Peptide Neoantigens and Stimulator of Interferon Genes Agonists Enhances Response to Cancer Vaccines

Cancer vaccines targeting patient-specific neoantigens have emerged as a promising strategy for improving responses to immune checkpoint blockade. However, neoantigenic peptides are poorly immunogenic and inept at stimulating CD8+ T cell responses, motivating a need for new vaccine technologies that enhance their immunogenicity. The stimulator of interferon genes (STING) pathway is an endogenous mechanism by which the innate immune system generates an immunological context for priming and mobilizing neoantigen-specific T cells. Owing to this critical role in tumor immune surveillance, a synthetic cancer nanovaccine platform (nanoSTING-vax) was developed that mimics immunogenic cancer cells in its capacity to efficiently promote co-delivery of peptide antigens and the STING agonist, cGAMP. The co-loading of cGAMP and peptides into pH-responsive, endosomolytic polymersomes promoted the coordinated delivery of both cGAMP and peptide antigens to the cytosol, thereby eliciting inflammatory cytokine production, co-stimulatory marker expression, and antigen cross-presentation. Consequently, nanoSTING-vax significantly enhanced CD8+ T cell responses to a range of peptide antigens. Therapeutic immunization with nanoSTING-vax, in combination with immune checkpoint blockade, inhibited tumor growth in multiple murine tumor models, even leading to complete tumor rejection and generation of durable antitumor immune memory. Collectively, this work establishes nanoSTING-vax as a versatile platform for enhancing immune responses to neoantigen-targeted cancer vaccines.

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:14

Enthalten in:

ACS nano - 14(2020), 8 vom: 25. Aug., Seite 9904-9916

Sprache:

Englisch

Beteiligte Personen:

Shae, Daniel [VerfasserIn]
Baljon, Jessalyn J [VerfasserIn]
Wehbe, Mohamed [VerfasserIn]
Christov, Plamen P [VerfasserIn]
Becker, Kyle W [VerfasserIn]
Kumar, Amrendra [VerfasserIn]
Suryadevara, Naveenchandra [VerfasserIn]
Carson, Carcia S [VerfasserIn]
Palmer, Christian R [VerfasserIn]
Knight, Frances C [VerfasserIn]
Joyce, Sebastian [VerfasserIn]
Wilson, John T [VerfasserIn]

Links:

Volltext

Themen:

9008-11-1
Antigens, Neoplasm
Cancer Vaccines
Cancer vaccine
Immune checkpoint blockade
Immunotherapy
Interferons
Journal Article
Neoantigen
Peptides
Polymer nanoparticle
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Anmerkungen:

Date Completed 14.05.2021

Date Revised 26.08.2021

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1021/acsnano.0c02765

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM312773099