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Adv. Healthc. Mater., Nov 06 2023, | https://doi.org/10.1002/adhm.202300549 Liposomal Delivery of an Immunostimulatory Cpg Induces Robust Antitumor Immunity and Long-Term Immune Memory by Reprogramming Tumor-Associated Macrophages

Yujin Kim^1,2, Seojung Lee ^1,2, Sangyong Jon ^1,2

¹Department of Biological Sciences, KAIST Institute for the BioCentury, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Daejeon, 34 141, Republic of Korea.

²Center for Precision Bio-Nanomedicine, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Daejeon, 34 141, Republic of Korea.

*Y. Kim and S. Jon are the co-corresponding authors of this work.

CORRESPONDING AUTHORS : Yujin Kim, Sangyong Jon

Abstract

Tumor-associated macrophages (TAMs)-representative immune-suppressive cells in the tumor microenvironment (TME)-are known to promote tumor progression and metastasis, and thus have been considered an attractive target for cancer therapy. However, current TAM-targeting strategies are insufficient to result in robust antitumor efficacy. Here, we report a small lipid nanoparticle encapsulating immunostimulatory CpG oligodeoxynucleotides (SLNP@CpG) as a new immunotherapeutic modality that can reprogram TAMs and further bridge innate-to-adaptive immunity. We found that SLNP@CpG treatment enhanced macrophage-mediated phagocytosis of cancer cells and tumor antigen cross-presentation and skewed the polarization state of macrophages in vitro. Intratumoral injection of SLNP@CpG into an established murine E.G7-OVA tumor model significantly suppressed tumor growth and considerably prolonged survival, completely eradicating tumors in 83.3% of mice. Furthermore, tumor-free mice resisted rechallenge with E.G7-OVA cancer cells through induction of immunological memory and long-term antitumor immunity. SLNP@CpG even exerted antitumor efficacy in an aggressive B16-F10 melanoma model by remodeling TME towards immune stimulation and tumor elimination. These findings suggest that, by modulating the function of TAMs and reshaping an immunosuppressive TME, the SLNP@CpG nanomedicine developed here may become a promising immunotherapeutic option applicable to a variety of tumors. This article is protected by copyright. All rights reserved.

논문정보

형식Research article
게재일2023년 11월 (BRIC 등록일 2023-11-09)
연구진국내 연구진
분야 바이오·의료융합 > 바이오센싱 및 나노바이오물질

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