Nanomaterials‐Mediated Co‐Stimulation of Toll‐Like Receptors and CD40 for Antitumor Immunity
Source abstract
Abstract
Abstract Toll‐like receptors (TLRs) and CD40‐related signaling pathways represent critical bridges between innate and adaptive immune responses. Here, an immunotherapy regimen that enables co‐stimulation of TLR7/8‐ and CD40‐mediated pathways is developed. TLR7/8 agonist resiquimod (R848) derived amino lipids, RAL1 and RAL2, are synthesized and 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%) and in vivo (61.3 ± 16.4%). When combined with agonistic anti‐CD40 antibody, this approach can produce effective antitumor activities in mouse melanoma tumor models, thereby suppressing tumor growth, prolonging mouse survival, and establishing antitumor memory immunity. Overall, RAL2‐LNPs provide a novel platform toward cancer immunotherapy by integrating innate and adaptive immunity.
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Research context
OpenAlex topics: Immunotherapy and Immune Responses · RNA Interference and Gene Delivery · Immune Response and Inflammation
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Division of Pharmaceutics & Pharmacology College of Pharmacy The Ohio State University Columbus OH 43210 USA
Center for Electron Microscopy and Analysis The Ohio State University Columbus OH 43212 USA
Department of Materials Science and Engineering The Ohio State University Columbus OH 43210 USA
Division of Medicinal Chemistry and Pharmacognosy College of Pharmacy The Ohio State University Columbus OH 43210 USA
Department of Radiation Oncology, Department of Biomedical Engineering The Center for Clinical and Translational Science The Comprehensive Cancer Center Dorothy M. Davis Heart & Lung Research Institute Center for Cancer Engineering, Center for Cancer Metabolism Pelotonia Institute for Immune‐Oncology The Ohio State University Columbus OH 43210 USA
Funding
National Institute of General Medical Sciences
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