Nanomaterials‐Mediated Co‐Stimulation of Toll‐Like Receptors and CD40 for Antitumor Immunity

• DOI: 10.1002/adma.202207486
• Publication Date: 2022-09-19T16:28:43Z
• Authors: Jingyue Yan; Yuebao Zhang; Shi Du; Xucheng Hou; Wenqing Li; Chunxi Zeng; Chengxiang Zhang; Jeffrey Cheng; Binbin Deng; David W. McComb; Weiyu Zhao; Yonger Xue; Diana D. Kang; Xiaolin Cheng; Yizhou Dong
• Keywords: TLR7; Cancer Immunotherapy

Abstract Toll‐like receptors (TLRs) and CD40‐related signaling pathways represent critical bridges between innate adaptive immune responses. Here, an immunotherapy regimen that enables co‐stimulation of TLR7/8‐ CD40‐mediated is developed. TLR7/8 agonist resiquimod (R848) derived amino lipids, RAL1 RAL2, are synthesized formulated into RAL‐derived lipid nanoparticles (RAL‐LNPs). The RAL2‐LNPs show efficient CD40 mRNA delivery to DCs both in vitro (90.8 ± 2.7%) vivo (61.3 16.4%). When combined with agonistic anti‐CD40 antibody, this approach can produce effective antitumor activities mouse melanoma tumor models, thereby suppressing growth, prolonging survival, establishing memory immunity. Overall, provide a novel platform toward cancer by integrating