web analytics

Nanovaccine That Activates The NLRP3 Inflammasome & Enhances Tumor Specific Activation Of Anti-Cancer Immunity

Published:
Lead Inventor: Aaron Esser-Kahn
Print or Save to PDF

SUMMARY

  • A major attention of vaccine adjuvant development has been focused on development of robust antibody-mediated protection against pathogens. However, such adjuvants have failed to elicit a robust T-cell mediated protection and are thus found to be less efficacious against diseases like malaria, tuberculosis, Ebola and Zika  or in immunotherapy.

  • Based on previous reports on the application of IL-1β in enhancing antigen-specific CD4+ and CD8+ responses, we envisioned that inflammasome-activating biomaterials that can produce IL-1β in-vivo can be potentially employed as vaccine adjuvants.

  • The faculty inventor developed a modulable inflammasome activating peptide agonist in a subunit-vaccine formulation along TLR 4 agonist in an oil-in-water emulsion. Further, since altered physico-chemical properties with other known agonists have been observed to induce significant differences in antigen-specific responses, they developed bio-materials by conjugating this peptide to a non-immunogenic polymer scaffold.

  • These biomaterials can be used as an additive (vaccine adjuvant) to enhance or modulate immune response to a vaccine in combination with other known conventional agonists.

 

FIGURE

Overview of the proposed mechanism of action of PAI nanovaccines based on mechanistic analyses herein. PAI nanovaccines enhance endocytosis by antigen-presenting cells on account of their ∼50 nm structure. Their secondary structure localizes effects to the injection site. Upon endocytosis, they then activate endosomal TLR7 and induce lysosomal rupture to result in NLRP3 inflammasome activation and cytosolic delivery of neoantigen to afford enhanced antigen presentation on MHC-I. When nanovaccines are injected peritumorally, they induce tumor localized, neoantigen-specific CD8+ T cell responses characterized by secretion of IFN-γ and GNZB to afford tumor clearance.

 

ADVANTAGES

ADVANTAGES

  • Enhancement of antigen‐specific T‐cells in response to vaccination

  • Reduced toxicity compared to other inflammasome-based approaches

 

APPLICATIONS

  • Immunotherapy
  • Modulation of immune response to vaccine
  • Treatment of viral ailments (e.g., malaria, tuberculosis, Ebola, and Zika)

PUBLICATIONS