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脂多糖A的抗肿瘤作用机制。

Mechanisms of the antitumoral effect of lipid A.

作者信息

Reisser Danièle, Pance Alena, Jeannin Jean-François

机构信息

Cancer Immunotherapy Research Laboratory, Ecole Pratique des Hautes Etudes, INSERM U517, Faculty of Medicine, 7 Boulevard Jeanne d'Arc, 21079 Dijon, France.

出版信息

Bioessays. 2002 Mar;24(3):284-9. doi: 10.1002/bies.10053.

Abstract

Bacterial lipopolysaccharide (LPS) and its active component, lipid A, have been used either alone or as adjuvant in therapeutic anticancer vaccines. Lipid A induces various transcription factors via intracellular signaling cascades initiated by their receptor CD14-TLR4. These events lead to the synthesis of cytokines, which either have direct cytotoxic effect or stimulate the immune system. Their antitumoral effect has been demonstrated in animal models as well as clinical trials. Studies in animal models showed that their antitumoral effect relies mostly on the generation of an effective immune response. In humans, the antitumoral effect was correlated with an antibody response and cell-mediated cytotoxicity. So far, some encouraging results have been achieved in phase I and II clinical trials with regards to response and stabilization of the disease, but an expansion of the studies and trials is needed to find the best conditions for their clinical application.

摘要

细菌脂多糖(LPS)及其活性成分脂质A已单独或作为佐剂用于治疗性抗癌疫苗。脂质A通过其受体CD14-TLR4启动的细胞内信号级联反应诱导各种转录因子。这些事件导致细胞因子的合成,细胞因子要么具有直接的细胞毒性作用,要么刺激免疫系统。它们的抗肿瘤作用已在动物模型以及临床试验中得到证实。动物模型研究表明,它们的抗肿瘤作用主要依赖于产生有效的免疫反应。在人类中,抗肿瘤作用与抗体反应和细胞介导的细胞毒性相关。到目前为止,在I期和II期临床试验中,在疾病反应和稳定方面已经取得了一些令人鼓舞的结果,但需要扩大研究和试验以找到其临床应用的最佳条件。

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