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- W2145969877 abstract "Dectin-1 is a pattern recognition receptor, which contributes to both innate and adaptive immunity against certain fungal and bacterial infections. Previously, we have shown that signals via Dectin-1 and TLR2 synergize to activate dendritic cells (DCs), resulting in decreased TH2 responses. In this study, we have made α-hDectin-1-Pam3CSK4 (Pam3) conjugate and tested its effectiveness in the suppression of TH2 responses in human in vitro and non-human primates (NHP) in vivo. An agonistic α-Dectin-1 antibody was chemically conjugated with Pam3. In human in vitro experiments, blood myeloid DCs (mDCs) were treated with α-Dectin-1-Pam3 in the presence or absence of TSLP. Phenotypes and functions of mDCs were assessed. In then NHP in vivo experiment, rhesus macaques were sensitized with house dust mite allergens and then treated with α-Dectin-1-Pam3. Serum IgE and skin reactions were assessed. Conjugating Pam3 to α-Dectin-1 antibody creates no alteration in α-hDectin Ab binding capacity to PBMCs. mDCs given α-hDectin-1-Pam3 can significantly decrease OX40L expression, even in the presence of TSLP, and can thus decrease Th2 responses, while slightly increasing IL-17 and IFNγ. Data from the NHP experiment, which is currently ongoing, will be discussed. Concomitant activation of DCs via Dectin-1 and TLR2 can significantly decrease TH2 responses while slightly enhancing TH1- and TH17 responses. This suggests that α-hDectin-pam3 conjugate could be a novel therapeutic candidate for TH2-driven inflammatory diseases, including allergy and allergic asthma as well as certain types of cancers." @default.
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- W2145969877 date "2015-02-01" @default.
- W2145969877 modified "2023-09-26" @default.
- W2145969877 title "Preclinical Assessment of the Effectiveness of α-Dectin-1-Pam3 Conjugate in Controlling TH2 Responses" @default.
- W2145969877 doi "https://doi.org/10.1016/j.jaci.2014.12.1264" @default.
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