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含 Zn 和 Mg 的三钙磷酸盐佐剂在癌症免疫治疗中的应用。

Zn- and Mg- containing tricalcium phosphates-based adjuvants for cancer immunotherapy.

机构信息

Human Technology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki, Japan.

出版信息

Sci Rep. 2013;3:2203. doi: 10.1038/srep02203.

Abstract

Zn-, and Mg-containing tricalcium phosphates (TCPs) loaded with a hydrothermal extract of a human tubercle bacillus (HTB) were prepared by immersing Zn-TCP and Mg-TCP in HTB-containing supersaturated calcium phosphate solutions. The in vitro and in vivo immunogenic activities of the HTB-loaded Zn-, and Mg-TCPs (Zn-Ap-HTB and Mg-Ap-HTB, respectively) were evaluated as potential immunopotentiating adjuvants for cancer immunotherapy. The Zn-Ap-HTB and Mg-Ap-HTB adjuvants showed no obvious cytotoxicity and more effectively stimulated granulocyte-macrophage colony-stimulating factor (GM-CSF) secretion by macrophage-like cells than unprocessed HTB or HTB-loaded TCP (T-Ap-HTB) in vitro. Zn-Ap-HTB and Mg-Ap-HTB mixed with liquid-nitrogen-treated tumor tissue markedly inhibited the in vivo development of rechallenged Lewis lung carcinoma (LLC) cells compared with T-Ap-HTB and the unprocessed HTB mixed liquid-nitrogen-treated tumor tissue. Zn-Ap-HTB and Mg-Ap-HTB contributed to eliciting potent systemic antitumor immunity in vivo.

摘要

负载有水热处理人结核杆菌(HTB)提取物的 Zn、Mg 三钙磷酸盐(TCP)是通过将 Zn-TCP 和 Mg-TCP 浸泡在含有 HTB 的过饱和磷酸钙溶液中制备的。将负载 HTB 的 Zn、Mg-TCP(分别为 Zn-Ap-HTB 和 Mg-Ap-HTB)作为癌症免疫治疗的潜在免疫佐剂,评估了其体外和体内的免疫原性活性。Zn-Ap-HTB 和 Mg-Ap-HTB 佐剂在体外没有明显的细胞毒性,并且比未经处理的 HTB 或负载 HTB 的 TCP(T-Ap-HTB)更有效地刺激巨噬细胞样细胞分泌粒细胞-巨噬细胞集落刺激因子(GM-CSF)。Zn-Ap-HTB 和 Mg-Ap-HTB 与液氮处理的肿瘤组织混合,与 T-Ap-HTB 和未经处理的 HTB 混合液氮处理的肿瘤组织相比,显著抑制了再挑战的 Lewis 肺癌(LLC)细胞在体内的发展。Zn-Ap-HTB 和 Mg-Ap-HTB 有助于在体内引发有效的全身抗肿瘤免疫。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc32/3712317/7c9bb017706a/srep02203-f1.jpg

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