Supramolecular Assembly of Toll-like Receptor 7/8 Agonist into Multimeric Water-Soluble Constructs Enables Superior Immune Stimulation In Vitro and In Vivo
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Porcine Red Blood Cells Packed 10% from Innovative Research was used in the following study:
Alexander K. Andrianov, Alexander Marin, Ruixue Wang, Hatice Karauzum, Ananda Chowdhury, Pragati Agnihotri, Abdul S. Yunus, Roy A. Mariuzza, and Thomas R. Fuerst
ACS Applied Bio Materials
April 8, 2020
The magnitude to which a pathogen triggers an immune response depends largely on the activation of specific pattern recognition receptors (PRR), particularly Toll-like receptors (TLRs), expressed by cells at the infection site. TLR7/8 agonists have the potential to fill clinical needs and are increasingly reaching advanced stages of development, as studies have shown that activation of these receptors stimulates development of cytotoxic T-cell responses that block the functions of immunosuppressive cells.
Resiquimod (R848 or RSQD) is a TLR7/8 agonist that shows promise as a vaccine because of its potential to promote cellular immunity. The development of this small molecule has been difficult because of its rapid in vivo clearance and lack of association with vaccine antigens. This study introduced a new approach in which a potent TLR7/8 agonist drug (RSQD) self-assembles with a biodegradable polyphosphazene polyelectrolyte (PCPP) in the multimeric form (PCPP-R) via ion pairing. The resulting noncovalent supramolecular construct is water-soluble and has superior immune stimulating activity in vitro when compared to a monomeric form of RSQD.
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Innovative Grade US Origin Bovine Whole Blood