Laboratory of Experimental Immunology, Institute of Microbiology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria.
Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., bl. 9, 1113 Sofia, Bulgaria.
Int Immunopharmacol. 2020 Jul;84:106566. doi: 10.1016/j.intimp.2020.106566. Epub 2020 May 18.
Various natural compounds have been tested as anticancer therapeutics in clinical trials. Most promising direction for antitumor therapy is the use of substances which enhance the immune system response stimulating tumor-specific lymphocytes. Hemocyanins are large extracellular oxygen transport glycoproteins isolated from different arthropod and mollusk species which exhibit strong anticancer properties. Immunized in mammals they trigger Th1 immune response that promotes unspecific stimulation and adjuvant activity in experimental therapeutic vaccines for cancer and antibody development. In the present study we used two hemocyanins - one isolated from marine snail Rapana thomasiana (RtH) and another one, from the terrestrial snail Helix pomatia (HpH) which have been investigated by using different administration schedules (intensive and mild) in murine model of colon carcinoma. The treatment with RtH and HpH generated high levels of antitumor IgG antibodies, antibody-producing plasma cells and tumor-specific CTLs, stimulated secretion of proinflammatory cytokines, suppressed the manifestation of carcinoma symptoms as tumor growth and size, and prolonged the life span of treated mice. Our results showed a significant anti-cancer effect of RtH and HpH hemocyanins on a murine model of colon carcinoma with promising potential for immunotherapy in various schemes of administration based on cross-reactive tumor-associated epitopes.
各种天然化合物已在临床试验中被测试作为抗癌治疗药物。最有前途的抗肿瘤治疗方向是使用增强免疫系统反应刺激肿瘤特异性淋巴细胞的物质。血蓝蛋白是从不同的节肢动物和软体动物物种中分离出来的大型细胞外氧运输糖蛋白，具有很强的抗癌特性。在哺乳动物中免疫后，它们会引发 Th1 免疫反应，促进癌症实验治疗疫苗和抗体开发中的非特异性刺激和佐剂活性。在本研究中，我们使用了两种血蓝蛋白 - 一种从海洋蜗牛 Rapana thomasiana（RtH）中分离出来，另一种从陆地蜗牛 Helix pomatia（HpH）中分离出来，我们使用不同的给药方案（强化和温和）在结肠癌的小鼠模型中进行了研究。用 RtH 和 HpH 治疗会产生高水平的抗肿瘤 IgG 抗体、产生抗体的浆细胞和肿瘤特异性 CTL，刺激促炎细胞因子的分泌，抑制癌症状的表现，如肿瘤生长和大小，并延长了治疗小鼠的寿命。我们的研究结果表明，RtH 和 HpH 血蓝蛋白对结肠癌的小鼠模型具有显著的抗癌作用，具有基于交叉反应性肿瘤相关表位的各种给药方案的免疫治疗的潜在前景。
