Co-delivery of Peptide Neoantigens and Stimulator of Interferon Genes Agonists Enhances Response to Cancer Vaccines
| Autor: | Mohamed Wehbe, Plamen P. Christov, Carcia S. Carson, Jessalyn J. Baljon, Kyle W. Becker, Christian R. Palmer, Sebastian Joyce, Frances C. Knight, Naveenchandra Suryadevara, Amrendra Kumar, John T. Wilson, Daniel Shae |
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| Rok vydání: | 2020 |
| Předmět: |
medicine.medical_treatment
T cell General Physics and Astronomy 02 engineering and technology Biology 010402 general chemistry Cancer Vaccines 01 natural sciences Article Mice Immune system Antigen Antigens Neoplasm Neoplasms medicine Animals Humans General Materials Science Innate immune system General Engineering Immunotherapy 021001 nanoscience & nanotechnology Immune checkpoint 3. Good health 0104 chemical sciences medicine.anatomical_structure Stimulator of interferon genes Cancer research Interferons Cancer vaccine Peptides 0210 nano-technology |
| Zdroj: | ACS Nano |
| ISSN: | 1936-086X 1936-0851 |
| Popis: | 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, costimulatory 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. |
| Databáze: | OpenAIRE |
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