Macrophage-targeted therapy: CD64-based immunotoxins for treatment of chronic inflammatory diseases.

Macrophage-targeted therapy: CD64-based immunotoxins for treatment of chronic inflammatory diseases.
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巨噬细胞靶向疗法:基于CD64的免疫毒素,用于治疗慢性炎性疾病。

DOI:
10.3390/toxins4090676
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发表时间:
2012-09
期刊:
影响因子:
4.2
通讯作者:
Thepen T
Thepen T
中科院分区:
医学2区
文献类型:
--
作者:
Hristodorov D;Mladenov R;Huhn M;Barth S;Thepen T

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慢性炎症引起的疾病(如关节炎、多发性硬化症和糖尿病性溃疡)是多起因的,因此治疗困难且效率低下。由于大多数这些疾病与年龄有关的性质以及人口向总体老年人口的转变,在不久的将来将需要制定有效的治疗干预策略。在过去的几十年里,在动物模型中,使用靶向cd64的免疫毒素消除活化的巨噬细胞已被证明是一种很有前途的解决炎症的方法。最近的数据表明,活化巨噬细胞的m1极化群体在慢性期尤为重要。我们概述资讯科技发展的最新进展。这些抗体已经从与细菌毒素化学偶联的全长抗体发展到与完全人类酶基因融合的单链抗体变体。这些改进增加了可能的目标疾病范围,现在包括慢性炎症性疾病。目前尚无针对巨噬细胞治疗慢性疾病的治疗策略。在这篇综述中,我们重点关注不同极化巨噬细胞的作用和cd64基IT在慢性炎症过程中的干预潜力。
Diseases caused by chronic inflammation (e.g., arthritis, multiple sclerosis and diabetic ulcers) are multicausal, thus making treatment difficult and inefficient. Due to the age-associated nature of most of these disorders and the demographic transition towards an overall older population, efficient therapeutic intervention strategies will need to be developed in the near future. Over the past decades, elimination of activated macrophages using CD64-targeting immunotoxins has proven to be a promising way of resolving inflammation in animal models. More recent data have shown that the M1-polarized population of activated macrophages in particular is critically involved in the chronic phase. We recapitulate the latest progress in the development of IT. These have advanced from full-length antibodies, chemically coupled to bacterial toxins, into single chain variants of antibodies, genetically fused with fully human enzymes. These improvements have increased the range of possible target diseases, which now include chronic inflammatory diseases. At present there are no therapeutic strategies focusing on macrophages to treat chronic disorders. In this review, we focus on the role of different polarized macrophages and the potential of CD64-based IT to intervene in the process of chronic inflammation.
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