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新型TLR2/3激动剂L-Pampo™通过激活引流淋巴结树突状细胞,作为一种有效的癌症疫苗佐剂发挥作用。

L-Pampo™, a Novel TLR2/3 Agonist, Acts as a Potent Cancer Vaccine Adjuvant by Activating Draining Lymph Node Dendritic Cells.

作者信息

Heo Yoonki, Ko Eunbyeol, Park Sejung, Park Si-On, Ahn Byung-Cheol, Yum Jung-Sun, Chun Eunyoung

机构信息

R&D Center, CHA Vaccine Institute, Seongnam-si 13493, Republic of Korea.

出版信息

Cancers (Basel). 2023 Aug 4;15(15):3978. doi: 10.3390/cancers15153978.

DOI:10.3390/cancers15153978
PMID:37568794
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10417701/
Abstract

TLR agonists have emerged as an efficient cancer vaccine adjuvant system that induces robust immune responses. L-pampo™, a proprietary vaccine adjuvant of TLR2 and TLR3 agonists, promotes strong humoral and cellular immune responses against infectious diseases. In this study, we demonstrate that vaccines formulated with L-pampo™ affect the recruitment and activation of dendritic cells (DCs) in draining lymph nodes (dLNs) and leading to antigen-specific T-cell responses and anti-tumor efficacy. We analyzed DC maturation and T-cell proliferation using flow cytometry and ELISA. We determined the effect of L-pampo™ on DCs in dLNs and antigen-specific T-cell responses using flow cytometric analysis and the ELISPOT assay. We employed murine tumor models and analyzed the anti-tumor effect of L-pampo™. We found that L-pampo™ directly enhanced the maturation and cytokine production of DCs and, consequently, T-cell proliferation. OVA or OVA peptide formulated with L-pampo™ promoted DC migration into dLNs and increased activation markers and specific DC subsets within dLNs. In addition, vaccines admixed with L-pampo™ promoted antigen-specific T-cell responses and anti-tumor efficacy. Moreover, the combination of L-pampo™ with an immune checkpoint inhibitor synergistically improved the anti-tumor effect. This study suggests that L-pampo™ can be a potent cancer vaccine adjuvant and a suitable candidate for combination immunotherapy.

摘要

Toll样受体(TLR)激动剂已成为一种能诱导强烈免疫反应的高效癌症疫苗佐剂系统。L-pampo™是一种TLR2和TLR3激动剂的专利疫苗佐剂,可促进针对传染病的强大体液免疫和细胞免疫反应。在本研究中,我们证明用L-pampo™配制的疫苗会影响引流淋巴结(dLN)中树突状细胞(DC)的募集和激活,并导致抗原特异性T细胞反应和抗肿瘤功效。我们使用流式细胞术和酶联免疫吸附测定(ELISA)分析DC成熟和T细胞增殖。我们通过流式细胞术分析和酶联免疫斑点测定(ELISPOT)确定L-pampo™对dLN中DC和抗原特异性T细胞反应的影响。我们采用小鼠肿瘤模型并分析L-pampo™的抗肿瘤作用。我们发现L-pampo™直接增强DC的成熟和细胞因子产生,从而促进T细胞增殖。用L-pampo™配制的卵清蛋白(OVA)或OVA肽可促进DC迁移到dLN中,并增加dLN内的激活标志物和特定DC亚群。此外,与L-pampo™混合的疫苗可促进抗原特异性T细胞反应和抗肿瘤功效。而且,L-pampo™与免疫检查点抑制剂联合使用可协同提高抗肿瘤效果。本研究表明,L-pampo™可以成为一种有效的癌症疫苗佐剂,也是联合免疫疗法的合适候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce6b/10417701/391b519aea88/cancers-15-03978-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce6b/10417701/6de2ba3d5971/cancers-15-03978-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce6b/10417701/ff448d767e3c/cancers-15-03978-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce6b/10417701/652292a6220a/cancers-15-03978-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce6b/10417701/fdc2eeb42cc4/cancers-15-03978-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce6b/10417701/772da5fecefb/cancers-15-03978-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce6b/10417701/391b519aea88/cancers-15-03978-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce6b/10417701/6de2ba3d5971/cancers-15-03978-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce6b/10417701/ff448d767e3c/cancers-15-03978-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce6b/10417701/652292a6220a/cancers-15-03978-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce6b/10417701/fdc2eeb42cc4/cancers-15-03978-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce6b/10417701/772da5fecefb/cancers-15-03978-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce6b/10417701/391b519aea88/cancers-15-03978-g006.jpg

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