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刚地弓形虫RH株衍生抗原对艾氏实体瘤的预防性抗肿瘤活性及通过比较免疫印迹法证明的共享抗原

Prophylactic antineoplastic activity of Toxoplasma gondii RH derived antigen against ehrlich solid carcinoma with evidence of shared antigens by comparative immunoblotting.

作者信息

Eissa Maha M, Gaafar Maha R, Younis Layla K, Ismail Cherine A, El Skhawy Nahla

机构信息

Department of Medical Parasitology, Faculty of Medicine, Alexandria University, Alexandria, Egypt.

Department of Pathology, Faculty of Medicine, Alexandria University, Alexandria, Egypt.

出版信息

Infect Agent Cancer. 2023 Apr 7;18(1):21. doi: 10.1186/s13027-023-00500-3.

Abstract

BACKGROUND

With cancer cases escalation, an urgent request to develop novel combating strategies arise. Pathogen-based cancer-immunotherapy is getting more consideration. Autoclaved parasitic antigens seem promising candidates, taking steadily their first steps. Our aim was to examine the prophylactic antineoplastic activity of autoclaved Toxoplasma vaccine (ATV) and to test for the shared antigen theory between Toxoplasma gondii and cancer cells.

METHODS

Mice were immunized with ATV followed by Ehrlich solid carcinoma (ESC) inoculation. Tumor weight, volume, histopathology, and immunohistochemistry for CD8 T cells, Treg cells and VEGF were assessed. In addition, the proposed shared antigen theory between parasites and cancer was also verified using SDS-PAGE and immunoblotting.

RESULTS

Results revealed powerful prophylactic activity of ATV with 13.3% inhibition of ESC incidence, significant reduction in tumor weight and volume in ATV vaccinated mice. Immunologically, significantly higher CD8T cells and lower FOXP3 Treg cells surrounded and infiltrated ESC in ATV immunized mice with higher CD8T/Treg cells ratio and significant antiangiogenic effect. Moreover, SDS-PAGE and immunoblotting showed four shared bands between Ehrlich carcinoma and ATV of approximate molecular weights 60, 26, 22 and 12.5 KDa.

CONCLUSION

Exclusively, we demonstrated a prophylactic antineoplastic activity of autoclaved Toxoplasma vaccine against ESC. Moreover, to the best of our knowledge this is the first report highlighting the existence of cross-reactive antigens between Toxoplasma gondi parasite and cancer cells of Ehrlich carcinoma.

摘要

背景

随着癌症病例的增加,迫切需要开发新的抗癌策略。基于病原体的癌症免疫疗法越来越受到关注。经高压灭菌的寄生虫抗原似乎是很有前景的候选物,并正在稳步迈出第一步。我们的目的是研究经高压灭菌的弓形虫疫苗(ATV)的预防性抗肿瘤活性,并测试弓形虫与癌细胞之间的共同抗原理论。

方法

用ATV免疫小鼠,然后接种艾氏实体癌(ESC)。评估肿瘤重量、体积、组织病理学以及CD8 T细胞、调节性T细胞(Treg细胞)和血管内皮生长因子(VEGF)的免疫组织化学。此外,还使用十二烷基硫酸钠-聚丙烯酰胺凝胶电泳(SDS-PAGE)和免疫印迹法验证了寄生虫与癌症之间提出的共同抗原理论。

结果

结果显示ATV具有强大的预防活性,可抑制13.3%的ESC发病率,显著降低接种ATV小鼠的肿瘤重量和体积。在免疫方面,在接种ATV的小鼠中,有显著更多的CD8 T细胞和更少的FOXP3 Treg细胞包围并浸润ESC,CD8 T/Treg细胞比率更高,且具有显著的抗血管生成作用。此外,SDS-PAGE和免疫印迹显示艾氏癌与ATV之间有四条分子量约为60、26、22和12.5 kDa的共同条带。

结论

我们首次证明了经高压灭菌的弓形虫疫苗对ESC具有预防性抗肿瘤活性。此外,据我们所知,这是第一份强调弓形虫寄生虫与艾氏癌癌细胞之间存在交叉反应性抗原的报告。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fddb/10082516/5cdd8969d07b/13027_2023_500_Fig1_HTML.jpg

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