研究动态
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软体动物血蓝蛋白在黑色素瘤小鼠模型中的免疫治疗潜力。

Immunotherapeutic Potential of Mollusk Hemocyanins in Murine Model of Melanoma.

发表日期:2024 May 15
作者: Emiliya Stoyanova, Nikolina Mihaylova, Nikola Ralchev, Silviya Bradyanova, Iliyan Manoylov, Yuliana Raynova, Krassimira Idakieva, Andrey Tchorbanov
来源: Marine Drugs

摘要:

抗肿瘤药物和疗法的开发需要新的方法和分子,而天然来源的产品为抗肿瘤研究提供了有趣的替代方案。腹足纲血蓝蛋白-多聚体含铜糖蛋白已用于许多癌症模型中的治疗性疫苗和抗肿瘤剂。我们通过用 B16F10 细胞系挑战 C57BL/6 小鼠以在实验动物中形成实体瘤,建立了黑色素瘤小鼠模型。在该黑色素瘤模型中,使用各种治疗方案评估了从海洋蜗牛 Rapana thomasiana (RtH) 和陆生蜗牛 Helix aspersa (HaH) 中分离出的血蓝蛋白的抗癌特性。还进行了流式细胞术、ELISA、增殖和细胞毒性测定以及组织学研究。观察了施用 RtH 或 HaH 后对荷瘤 C​​57BL/6 小鼠的肿瘤生长、肿瘤发生率和存活率的有益影响。高滴度的黑色素瘤特异性 IgM 抗体、促炎细胞因子和肿瘤特异性 CTL 以及高水平的肿瘤浸润 M1 巨噬细胞的产生增强了免疫反应和肿瘤抑制。RtH 和 HaH 都表现出了有前景的应用特性抗肿瘤治疗剂和未来的人体实验。
The development of antitumor drugs and therapy requires new approaches and molecules, and products of natural origin provide intriguing alternatives for antitumor research. Gastropodan hemocyanins-multimeric copper-containing glycoproteins have been used in therapeutic vaccines and antitumor agents in many cancer models.We established a murine model of melanoma by challenging C57BL/6 mice with a B16F10 cell line for solid tumor formation in experimental animals. The anticancer properties of hemocyanins isolated from the marine snail Rapana thomasiana (RtH) and the terrestrial snail Helix aspersa (HaH) were evaluated in this melanoma model using various schemes of therapy. Flow cytometry, ELISA, proliferation, and cytotoxicity assays, as well as histology investigations, were also performed.Beneficial effects on tumor growth, tumor incidence, and survival of tumor-bearing C57BL/6 mice after administration of the RtH or HaH were observed. The generation of high titers of melanoma-specific IgM antibodies, pro-inflammatory cytokines, and tumor-specific CTLs, and high levels of tumor-infiltrated M1 macrophages enhanced the immune reaction and tumor suppression.Both RtH and HaH exhibited promising properties for applications as antitumor therapeutic agents and future experiments with humans.