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对晚期转移性癌症的有效免疫排斥

Effective immune rejection of advanced metastasized cancer.

作者信息

Schirrmacher V, Beckhove P, Kruger A, Rocha M, Umansky V, Fichtner K, Hull W, Zangemeisterwittke U, Griesbach A, Jurianz K, Vonhoegen P

机构信息

DEUTSCH KREBSFORSCHUNGSZENTRUM,ZENT SPEKT,HEIDELBERG,GERMANY.

出版信息

Int J Oncol. 1995 Mar;6(3):505-21. doi: 10.3892/ijo.6.3.505.

DOI:10.3892/ijo.6.3.505
PMID:21556565
Abstract

A cellular cancer therapy is described with unique efficiency even in late-stage disease. in situ activated tumor-immune T cells, induced in allogeneic, tumor-resistant, MHC identical but superantigen different donor mice (B10.D2) could transfer strong graft-versus-leukemia (GvL) effects accompanied by only mild graft-versus-host (GvH) reactivity. Systemic immune cell transfer into 5 Gy irradiated DBA/2 mice bearing up to 4 week established syngeneic tumors and macrometastases led to massive infiltration of tumor tissues by CD4 and CD8 donor T lymphocytes. Upon interaction of immune CD4 donor T cells with host antigen presenting cells in synergy with immune CD8 donor T cells attacking the tumor cells directly, primary tumors (1.5 cm diameter) were encapsulated and rejected from the skin and liver metastases eradicated. For the first time, such adoptive cellular immunotherapy (ADI) was followed in individual live animals by P-31-NMR spectroscopy of primary tumors. An approximately 25,000 fold excess of metastatic tumor cells could be rejected as revealed quantitatively by FACScan analysis of lacZ gene transfected tumor cells.

摘要

一种细胞癌症疗法被描述为即使在疾病晚期也具有独特的疗效。在同种异体、肿瘤抗性、MHC相同但超抗原不同的供体小鼠(B10.D2)中诱导产生的原位活化肿瘤免疫T细胞,可传递强大的移植物抗白血病(GvL)效应,同时仅伴有轻微的移植物抗宿主(GvH)反应性。将全身免疫细胞转移到接受5 Gy照射、患有长达4周已形成的同基因肿瘤和大转移灶的DBA/2小鼠体内,导致肿瘤组织被CD4和CD8供体T淋巴细胞大量浸润。当免疫CD4供体T细胞与宿主抗原呈递细胞相互作用,并与直接攻击肿瘤细胞的免疫CD8供体T细胞协同作用时,原发性肿瘤(直径1.5厘米)被包裹并从皮肤中排斥,肝转移灶被根除。首次在个体活体动物中通过对原发性肿瘤进行P-31-NMR光谱分析来跟踪这种过继性细胞免疫疗法(ADI)。通过对lacZ基因转染肿瘤细胞的FACScan分析定量显示,大约25000倍过量的转移性肿瘤细胞可被排斥。

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Mitochondria at Work: New Insights into Regulation and Dysregulation of Cellular Energy Supply and Metabolism.线粒体的作用:细胞能量供应与代谢调节及失调的新见解
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Cancer Vaccines and Oncolytic Viruses Exert Profoundly Lower Side Effects in Cancer Patients than Other Systemic Therapies: A Comparative Analysis.
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From chemotherapy to biological therapy: A review of novel concepts to reduce the side effects of systemic cancer treatment (Review).从化疗到生物疗法:减少全身癌症治疗副作用的新概念综述(综述)。
Int J Oncol. 2019 Feb;54(2):407-419. doi: 10.3892/ijo.2018.4661. Epub 2018 Dec 10.
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Complete remission of cancer in late-stage disease by radiation and transfer of allogeneic MHC-matched immune T cells: lessons from GvL studies in animals.通过放疗和同种异体 MHC 匹配免疫 T 细胞移植使晚期癌症完全缓解:来自动物 GvL 研究的经验。
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