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在小鼠Lewis肺癌模型中,术后使用鸡全胚疫苗进行无佐剂治疗性异种接种可抑制远处微转移并延长生存期。

Post-operative unadjuvanted therapeutic xenovaccination with chicken whole embryo vaccine suppresses distant micrometastases and prolongs survival in a murine Lewis lung carcinoma model.

作者信息

Kraśko Jan Aleksander, Žilionytė Karolina, Darinskas Adas, Dobrovolskienė Neringa, Mlynska Agata, Riabceva Svetlana, Zalutsky Iosif, Derevyanko Marina, Kulchitsky Vladimir, Karaman Olga, Fedosova Natalia, Symchych Tatiana Vasyliyvna, Didenko Gennady, Chekhun Vasyl, Strioga Marius, Pašukonienė Vita

机构信息

Laboratory of Immunology, National Cancer Institute, Vilnius, Vilnius LT-08660, Lithuania.

Department of Immunology, State Research Institute Centre for Innovative Medicine, Vilnius, Vilnius LT-08406, Lithuania.

出版信息

Oncol Lett. 2018 Apr;15(4):5098-5104. doi: 10.3892/ol.2018.7950. Epub 2018 Feb 5.

DOI:10.3892/ol.2018.7950
PMID:29552144
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5840525/
Abstract

Immunotherapy in the form of anticancer vaccination relies on the mobilization of the patient's immune system against specific cancer antigens. Instead of focusing on an autologous cell lysate, which is not always available in clinical practice, the present study investigates vaccines utilizing xenogeneic foetal tissue that are rich in oncofoetal antigens. Lewis lung carcinoma (LLC)-challenged C57BL/6 mice were treated with either a xenogeneic vaccine made from chicken whole embryo, or a xenogeneic vaccine made from rat embryonic brain tissue, supplemented with a protein fraction as an adjuvant. Median and overall survival, size of metastatic foci in lung tissue and levels of circulating CD8a T cells were evaluated and compared with untreated control mice. Following primary tumour removal, a course of three subcutaneous vaccinations with xenogeneic chicken embryo vaccine led to significant increase in overall survival rate (100% after 70 days of follow-up vs. 40% in untreated control mice), significant increase in circulating CD8a T cells (18.18 vs. 12.6% in untreated control mice), and a significant decrease in the area and incidence of metastasis foci. The xenogeneic rat brain tissue-based vaccine did not improve any of the investigated parameters, despite promising reports in other models. We hypothesize that the proper selection of antigen source (tissue) can constitute an effective immunotherapeutic product.

摘要

以抗癌疫苗形式进行的免疫疗法依赖于调动患者的免疫系统来对抗特定的癌症抗原。本研究并未聚焦于临床实践中并非总能获取的自体细胞裂解物,而是研究利用富含癌胚抗原的异种胎儿组织制成的疫苗。用鸡全胚胎制成的异种疫苗或用大鼠胚胎脑组织制成的异种疫苗(辅以一种蛋白质组分作为佐剂)对受Lewis肺癌(LLC)攻击的C57BL/6小鼠进行治疗。评估了中位生存期和总生存期、肺组织中转移灶的大小以及循环CD8a T细胞水平,并与未治疗的对照小鼠进行比较。在切除原发性肿瘤后,用异种鸡胚胎疫苗进行三个疗程的皮下接种,导致总生存率显著提高(随访70天后为100%,而未治疗的对照小鼠为40%),循环CD8a T细胞显著增加(18.18%,而未治疗的对照小鼠为12.6%),转移灶的面积和发生率显著降低。尽管在其他模型中有令人鼓舞的报道,但基于异种大鼠脑组织的疫苗并未改善任何所研究的参数。我们推测,抗原来源(组织)的恰当选择可以构成一种有效的免疫治疗产品。

相似文献

1
Post-operative unadjuvanted therapeutic xenovaccination with chicken whole embryo vaccine suppresses distant micrometastases and prolongs survival in a murine Lewis lung carcinoma model.在小鼠Lewis肺癌模型中,术后使用鸡全胚疫苗进行无佐剂治疗性异种接种可抑制远处微转移并延长生存期。
Oncol Lett. 2018 Apr;15(4):5098-5104. doi: 10.3892/ol.2018.7950. Epub 2018 Feb 5.
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本文引用的文献

1
Bacterial ghosts as adjuvants in syngeneic tumour cell lysate-based anticancer vaccination in a murine lung carcinoma model.在小鼠肺癌模型中,细菌幽灵作为基于同基因肿瘤细胞裂解物的抗癌疫苗接种的佐剂。
Oncol Rep. 2017 Jan;37(1):171-178. doi: 10.3892/or.2016.5252. Epub 2016 Nov 16.
2
Xenogeneic cell-based vaccine therapy for colorectal cancer: Safety, association of clinical effects with vaccine-induced immune responses.用于结直肠癌的基于异种细胞的疫苗疗法:安全性,临床疗效与疫苗诱导的免疫反应的关联
Biomed Pharmacother. 2016 Oct;83:1247-1252. doi: 10.1016/j.biopha.2016.08.050. Epub 2016 Aug 24.
3
Xenogeneic cell-based vaccine therapy for stage III melanoma: safety, immune-mediated responses and survival benefits.异体细胞为基础的疫苗治疗 III 期黑色素瘤:安全性、免疫介导的反应和生存获益。
Eur J Dermatol. 2016 Apr 1;26(2):138-43. doi: 10.1684/ejd.2016.2733.
4
Anticancer effectiveness of vaccination based on xenogeneic embryo proteins applied in different schedules.
Exp Oncol. 2015 Sep;37(3):197-202.
5
Cardamonin Inhibits Metastasis of Lewis Lung Carcinoma Cells by Decreasing mTOR Activity.小豆蔻明通过降低mTOR活性抑制Lewis肺癌细胞转移。
PLoS One. 2015 May 21;10(5):e0127778. doi: 10.1371/journal.pone.0127778. eCollection 2015.
6
Antibody response to cancer/testis (CT) antigens: A prognostic marker in cancer patients.针对癌症/睾丸(CT)抗原的抗体反应:癌症患者的预后标志物。
Oncoimmunology. 2014 Dec 21;3(11):e970032. doi: 10.4161/21624011.2014.970032. eCollection 2014 Nov.
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Classification of current anticancer immunotherapies.当前抗癌免疫疗法的分类。
Oncotarget. 2014 Dec 30;5(24):12472-508. doi: 10.18632/oncotarget.2998.
8
Therapeutic vaccines for cancer: an overview of clinical trials.癌症治疗性疫苗:临床试验概述。
Nat Rev Clin Oncol. 2014 Sep;11(9):509-24. doi: 10.1038/nrclinonc.2014.111. Epub 2014 Jul 8.
9
The anticancer efficiency of the xenogeneic vaccine and the indication for its use.
Exp Oncol. 2014 Jun;36(2):79-84.
10
Xenogeneic therapeutic cancer vaccines as breakers of immune tolerance for clinical application: to use or not to use?作为打破免疫耐受用于临床的异种治疗性癌症疫苗:用还是不用?
Vaccine. 2014 Jul 7;32(32):4015-24. doi: 10.1016/j.vaccine.2014.05.006. Epub 2014 May 14.