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  2. A nanoadjuvant that dynamically coordinates innate immune stimuli activation enhances cancer immunotherapy and reduces immune cell exhaustion

A nanoadjuvant that dynamically coordinates innate immune stimuli activation enhances cancer immunotherapy and reduces immune cell exhaustion

  • Nat Nanotechnol. 2023 Jan 12. doi: 10.1038/s41565-022-01296-w.
Seung Mo Jin # 1 Yeon Jeong Yoo # 1 Hong Sik Shin 1 Sohyun Kim 1 Sang Nam Lee 1 Chang Hoon Lee 1 Hyunji Kim 1 Jung-Eun Kim 1 Yong-Soo Bae 2 JungHyub Hong 2 Young-Woock Noh 3 Yong Taik Lim 4
Affiliations

Affiliations

  • 1 SKKU Advanced Institute of Nanotechnology (SAINT), Department of Nano Science and Technology, Department of Nano Engineering, School of Chemical Engineering, and Biomedical Institute for Convergence at SKKU, Sungkyunkwan University, Suwon, Republic of Korea.
  • 2 Department of Biological Sciences, Science Research Center (SRC) for Immune Research on Non-lymphoid Organ (CIRNO), Department of Biological Science, Sungkyunkwan University, Suwon, Republic of Korea.
  • 3 New Drug Development Center, Osong Medical Innovation Foundation, Cheongju, Republic of Korea.
  • 4 SKKU Advanced Institute of Nanotechnology (SAINT), Department of Nano Science and Technology, Department of Nano Engineering, School of Chemical Engineering, and Biomedical Institute for Convergence at SKKU, Sungkyunkwan University, Suwon, Republic of Korea. yongtaik@skku.edu.
  • # Contributed equally.
Abstract

Although conventional innate immune stimuli contribute to immune activation, they induce exhausted immune cells, resulting in suboptimal Cancer Immunotherapy. Here we suggest a kinetically activating nanoadjuvant (K-nanoadjuvant) that can dynamically integrate two waves of innate immune stimuli, resulting in effective antitumour immunity without immune cell exhaustion. The combinatorial code of K-nanoadjuvant is optimized in terms of the order, duration and time window between spatiotemporally activating Toll-like Receptor 7/8 agonist and other Toll-like Receptor agonists. K-nanoadjuvant induces effector/non-exhausted dendritic cells that programme the magnitude and persistence of interleukin-12 secretion, generate effector/non-exhausted CD8+ T cells, and activate natural killer cells. Treatment with K-nanoadjuvant as a monotherapy or in combination therapy with anti-PD-L1 or liposomes (doxorubicin) results in strong antitumour immunity in murine models, with minimal systemic toxicity, providing a strategy for synchronous and dynamic tailoring of innate immunity for enhanced Cancer Immunotherapy.

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