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吞噬细胞受体锚定激动剂在癌症免疫治疗中的应用：B16-F10小鼠黑色素瘤模型

The use of anchored agonists of phagocytic receptors for cancer immunotherapy: B16-F10 murine melanoma model.

作者信息

Janotová Tereza, Jalovecká Marie, Auerová Marie, Švecová Ivana, Bruzlová Pavlína, Maierová Veronika, Kumžáková Zuzana, Cunátová Štěpánka, Vlčková Zuzana, Caisová Veronika, Rozsypalová Petra, Lukáčová Katarína, Vácová Nikol, Wachtlová Markéta, Salát Jiří, Lieskovská Jaroslava, Kopecký Jan, Ženka Jan

机构信息

Department of Medical Biology, Faculty of Science, University of South Bohemia, České Budějovice, Czech Republic.

Department of Pathology, Regional Hospital, České Budějovice, Czech Republic.

出版信息

PLoS One. 2014 Jan 13;9(1):e85222. doi: 10.1371/journal.pone.0085222. eCollection 2014.

DOI:10.1371/journal.pone.0085222
PMID:24454822
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3890306/
Abstract

The application of the phagocytic receptor agonists in cancer immunotherapy was studied. Agonists (laminarin, molecules with terminal mannose, N-Formyl-methioninyl-leucyl-phenylalanine) were firmly anchored to the tumor cell surface. When particular agonists of phagocytic receptors were used together with LPS (Toll-like receptor agonist), high synergy causing tumour shrinkage and a temporary or permanent disappearance was observed. Methods of anchoring phagocytic receptor agonists (charge interactions, anchoring based on hydrophobic chains, covalent bonds) and various regimes of phagocytic agonist/LPS mixture applications were tested to achieve maximum therapeutic effect. Combinations of mannan/LPS and f-MLF/LPS (hydrophobic anchors) in appropriate (pulse) regimes resulted in an 80% and 60% recovery for mice, respectively. We propose that substantial synergy between agonists of phagocytic and Toll-like receptors (TLR) is based on two events. The TLR ligand induces early and massive inflammatory infiltration of tumors. The effect of this cell infiltrate is directed towards tumor cells, bearing agonists of phagocytic receptors on their surface. The result of these processes was effective killing of tumor cells. This novel approach represents exploitation of innate immunity mechanisms for treating cancer.

摘要

研究了吞噬细胞受体激动剂在癌症免疫治疗中的应用。激动剂（海带多糖、带有末端甘露糖的分子、N-甲酰甲硫氨酰亮氨酰苯丙氨酸）被牢固地锚定在肿瘤细胞表面。当吞噬细胞受体的特定激动剂与脂多糖（Toll样受体激动剂）一起使用时，观察到导致肿瘤缩小以及暂时或永久消失的高度协同作用。测试了吞噬细胞受体激动剂的锚定方法（电荷相互作用、基于疏水链的锚定、共价键）以及吞噬激动剂/脂多糖混合物的各种应用方案，以实现最大治疗效果。甘露聚糖/脂多糖和甲酰甲硫氨酰亮氨酰苯丙氨酸/脂多糖（疏水锚定）在适当（脉冲）方案下的组合分别使小鼠的恢复率达到80%和60%。我们提出，吞噬细胞和Toll样受体（TLR）激动剂之间的显著协同作用基于两个事件。TLR配体诱导肿瘤早期大量炎症浸润。这种细胞浸润的作用针对表面带有吞噬细胞受体激动剂的肿瘤细胞。这些过程的结果是有效杀死肿瘤细胞。这种新方法代表了利用先天免疫机制治疗癌症。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/467a/3890306/74ed88c5ea4a/pone.0085222.g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/467a/3890306/3ba3931f5987/pone.0085222.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/467a/3890306/8312eafd75c1/pone.0085222.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/467a/3890306/07e16aa0c423/pone.0085222.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/467a/3890306/2f96bac1c97f/pone.0085222.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/467a/3890306/f8765a7c32f7/pone.0085222.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/467a/3890306/7268b349b993/pone.0085222.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/467a/3890306/77a9b3f92b54/pone.0085222.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/467a/3890306/9486aaea73e1/pone.0085222.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/467a/3890306/8fa634ea8841/pone.0085222.g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/467a/3890306/74ed88c5ea4a/pone.0085222.g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/467a/3890306/3ba3931f5987/pone.0085222.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/467a/3890306/8312eafd75c1/pone.0085222.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/467a/3890306/07e16aa0c423/pone.0085222.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/467a/3890306/2f96bac1c97f/pone.0085222.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/467a/3890306/f8765a7c32f7/pone.0085222.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/467a/3890306/7268b349b993/pone.0085222.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/467a/3890306/77a9b3f92b54/pone.0085222.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/467a/3890306/9486aaea73e1/pone.0085222.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/467a/3890306/8fa634ea8841/pone.0085222.g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/467a/3890306/74ed88c5ea4a/pone.0085222.g010.jpg

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