Cyclic Amp-Elevating Drugs As Adjuvants - 2014-084
Where current adjuvants act by one or several of the following mechanisms, the Th17-class of adjuvants mediate all of the following: Increase antigen transport and uptake (phagocytosis) by antigen-presenting cells Provide a long-lasting depot effect, i.e., antigenic reservoir for slow release Trigger efficient antigen processing and presentation Induce co-stimulatory molecules and cytokine release by dendritic cells (necessary for the activation of naïve T cells) Provoke additional activation pathways (e.g., pattern-recognition receptors such as Toll-like receptors and the unfolded protein response pathway) These features combine with the simplicity of small molecules and the design of here-to-fore dissimilar vaccines for diverse applications.
This formulation of antigen-adjuvant-carrier is envisioned for use in vaccines that are:Delivered systemically or mucosally Therapeutic or prophylactic.
In foundational studies, UC researchers observed that cAMP production in a critical subpopulation of cells (i.e., dendritic cells) selectively activated cAMP/PKA pathway. This work has now been applied to the design and testing of a “universal vaccine” formulation, comprising an antigen of interest with a class of Th17 adjuvants and a carrier or additional adjuvant such as alum. The ability to target to the critical cell type enables a powerful adjuvant with improved toxicity profiles, Additionally, the focus on small (<1,000 Da MW), drug-like and non-immunogenic molecules should eliminate immunogenicity problems associated with bacterial polypeptides and biologic agents that raise cAMP levels via an irreversible mechanism.
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State Of Development Mice have been immunized and then early indicators of immune response assessed (IL-17 response and titer of Ab vs. immunogen (Anti-OVA IgG)). Intellectual Property Info US rights available for licensure. See “Patent Status”, below. Related Materials Related Technologies Tech ID/UC Case 25178/2011-208-0 Related Cases 2011-208-0, 2013-334-0, 2013-282-0
Lee J, et al., Cyclic AMP concentrations in dendritic cells induce and regulate Th2 immunity and allergic asthma, Proc Natl Acad Sci U S A. 2015, 3;112(5):1529-34.
González-Navajas JM, et al., The immediate protective response to microbial challenge, Eur J Immunol. 2014, 44(9):2536-49. Review.
Li, X., et al., Divergent requirement for Gas and cAMP in the differentiation and inflammatory profile of distinct mouse Th subsets, J Clin Invest., 2012, 122(3):963-73.
Pulendran B, et al., Programming dendritic cells to induce T(H)2 and tolerogenic responses. Nat Immunol, 2010, 11: 647-55
Datta SK, et al., Mucosal adjuvant activity of cholera toxin requires Th17 cells and protects against inhalation anthrax. Proc Natl Acad Sci U S A, 2010, 107: 10638-43
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