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

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

doi:10.1002/adma.202207486

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

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

Research output: Contribution to journal › Article › peer-review

32 Scopus citations

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.

Original language	English
Article number	2207486
Journal	Advanced Materials
Volume	34
Issue number	47
DOIs	https://doi.org/10.1002/adma.202207486
State	Published - 24 Nov 2022
Externally published	Yes

Keywords

CD40
immunotherapy
lipid nanoparticles
mRNA
resiquimod

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title = "Nanomaterials-Mediated Co-Stimulation of Toll-Like Receptors and CD40 for Antitumor Immunity",

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.",

keywords = "CD40, immunotherapy, lipid nanoparticles, mRNA, resiquimod",

author = "Jingyue Yan and Yuebao Zhang and Shi Du and Xucheng Hou and Wenqing Li and Chunxi Zeng and Chengxiang Zhang and Jeffrey Cheng and Binbin Deng and McComb, {David W.} and Weiyu Zhao and Yonger Xue and Kang, {Diana D.} and Xiaolin Cheng and Yizhou Dong",

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year = "2022",

month = nov,

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doi = "10.1002/adma.202207486",

language = "English",

volume = "34",

journal = "Advanced Materials",

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T1 - Nanomaterials-Mediated Co-Stimulation of Toll-Like Receptors and CD40 for Antitumor Immunity

AU - Yan, Jingyue

AU - Zhang, Yuebao

AU - Du, Shi

AU - Hou, Xucheng

AU - Li, Wenqing

AU - Zeng, Chunxi

AU - Zhang, Chengxiang

AU - Cheng, Jeffrey

AU - Deng, Binbin

AU - McComb, David W.

AU - Zhao, Weiyu

AU - Xue, Yonger

AU - Kang, Diana D.

AU - Cheng, Xiaolin

AU - Dong, Yizhou

PY - 2022/11/24

Y1 - 2022/11/24

N2 - 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.

AB - 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.

KW - CD40

KW - immunotherapy

KW - lipid nanoparticles

KW - mRNA

KW - resiquimod

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DO - 10.1002/adma.202207486

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SN - 0935-9648

VL - 34

JO - Advanced Materials

JF - Advanced Materials

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M1 - 2207486

ER -

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

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Keywords

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