Unleashing endogenous TNF-alpha as a cancer immunotherapeutic.
Unleashing endogenous TNF-alpha as a cancer immunotherapeutic.
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DOI：
10.1186/s12967-018-1611-7
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发表时间：
2018-08-31
影响因子：
7.4
通讯作者：
Jafri A
中科院分区：
文献类型：
--
作者：
Josephs SF;Ichim TE;Prince SM;Kesari S;Marincola FM;Escobedo AR;Jafri A
肿瘤坏死因子(TNF)- α最初在20世纪70年代被确定为先天性免疫的血清介质，能够诱导肿瘤出血性坏死。如今，该分子具有广泛的生物活性，临床转化主要不是用它来治疗癌症，而是抑制其治疗自身免疫的作用。利用全身性tnf - α给药的临床试验导致了不可接受的毒性水平，这阻碍了其发展。相比之下，以孤立肢体灌注形式局部给予tnf - α在软组织肉瘤中取得了良好的效果。在这里，我们描述了一种利用tnf - α的有效抗肿瘤活性的新方法，通过体外去除可溶性tnf - α受体来增强局部产生的tnf - α的活性。具体来说，我们知道癌组织被单核细胞、T细胞和其他能够产生tnf - α的细胞浸润。我们也知道肿瘤以及肿瘤微环境中的细胞会产生可溶性的tnf - α受体。作者认为，通过选择性地去除可溶性tnf - α受体，内源性tnf - α活性的局部增强可能会增强肿瘤细胞的死亡，而不会产生相关的全身毒性。
Tumor necrosis factor (TNF)-alpha was originally identified in the 1970s as the serum mediator of innate immunity capable of inducing hemorrhagic necrosis in tumors. Today, a wide spectrum of biological activities have been attributed to this molecule, and clinical translation has mainly occurred not in using it to treat cancer, but rather to inhibit its effects to treat autoimmunity. Clinical trials utilizing systemic TNF-alpha administration have resulted in an unacceptable level of toxicities, which blocked its development. In contrast, localized administration of TNF-alpha in the form of isolated limb perfusion have yielded excellent results in soft tissue sarcomas. Here we describe a novel approach to leveraging the potent antineoplastic activities of TNF-alpha by enhancing activity of locally produced TNF-alpha through extracorporeal removal of soluble TNF-alpha receptors. Specifically, it is known that cancerous tissues are infiltrated with monocytes, T cells, and other cells capable of producing TNF-alpha. It is also known that tumors, as well as cells in the tumor microenvironment produce soluble TNF-alpha receptors. The authors believe that by selectively removing soluble TNF-alpha receptors local enhancement of endogenous TNF-alpha activity may provide for enhanced tumor cell death without associated systemic toxicities.
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DOI：
10.1084/jem.20151563
发表时间：
2016-08-22
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Chopra M;Biehl M;Steinfatt T;Brandl A;Kums J;Amich J;Vaeth M;Kuen J;Holtappels R;Podlech J;Mottok A;Kraus S;Jordán-Garrote AL;Bäuerlein CA;Brede C;Ribechini E;Fick A;Seher A;Polz J;Ottmüller KJ;Baker J;Nishikii H;Ritz M;Mattenheimer K;Schwinn S;Winter T;Schäfer V;Krappmann S;Einsele H;Müller TD;Reddehase MJ;Lutz MB;Männel DN;Berberich-Siebelt F;Wajant H;Beilhack A
通讯作者：
Beilhack A
影响因子：
15.9
作者：
Aderka, D;Sorkine, P;Klausner, J
通讯作者：
Klausner, J
影响因子：
11.2
作者：
Ardestani S;Li B;Deskins DL;Wu H;Massion PP;Young PP
通讯作者：
Young PP
DOI：
10.1084/jem.169.6.1977
发表时间：
1989-06-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Brett J;Gerlach H;Nawroth P;Steinberg S;Godman G;Stern D
通讯作者：
Stern D
影响因子：
3.1
作者：
CLARK, IA;VIRELIZIER, JL;WOOD, PR
通讯作者：
WOOD, PR