2. Academic Validation
  3. Co-delivery of Peptide Neoantigens and Stimulator of Interferon Genes Agonists Enhances Response to Cancer Vaccines

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

  • ACS Nano. 2020 Aug 25;14(8):9904-9916. doi: 10.1021/acsnano.0c02765.
Daniel Shae 1,  Jessalyn J Baljon 2,  Mohamed Wehbe 1,  Plamen P Christov 3,  Kyle W Becker 1,  Amrendra Kumar 4 5,  Naveenchandra Suryadevara 4 5,  Carcia S Carson 2,  Christian R Palmer 1,  Frances C Knight 2,  Sebastian Joyce 4 5 6 7,  John T Wilson 1 2 3 4 5 6 7 8
Affiliations

Affiliations

  • 1 Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, Tennessee 37235, United States.
  • 2 Department of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee 37235, United States.
  • 3 Vanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, Tennessee 37232, United States.
  • 4 Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, United States.
  • 5 Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, Tennessee 37212, United States.
  • 6 Vanderbilt Institute for Infection, Immunology, and Inflammation, Vanderbilt University Medical Center, Nashville, Tennessee 37232, United States.
  • 7 Vanderbilt Center for Immunobiology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, United States.
  • 8 Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee 37232, United States.
PMID: 32701257 DOI: 10.1021/acsnano.0c02765
Abstract

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.

Keywords

cancer vaccine; immune checkpoint blockade; immunotherapy; neoantigen; polymer nanoparticle.

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