树突状细胞免疫疗法:临床结果。

Dendritic cell immunotherapy: clinical outcomes.

机构信息

College of Health and Biomedicine, Centre for Chronic Disease Prevention and Management, Victoria University , Melbourne, VIC, Australia.

BioOrganic and Medicinal Chemistry Laboratory, Centre for Biomedical Research, Burnet Institute , Melbourne, VIC, Australia ; Department of Pathology, University of Melbourne , Melbourne, VIC, Australia ; Department of Immunology, Monash University , Melbourne, VIC, Australia.

出版信息

Clin Transl Immunology. 2014 Jul 18;3(7):e21. doi: 10.1038/cti.2014.14. eCollection 2014 Jul.

Abstract

The use of tumour-associated antigens for cancer immunotherapy studies is exacerbated by tolerance to these self-antigens. Tolerance may be broken by using ex vivo monocyte-derived dendritic cells (DCs) pulsed with self-antigens. Targeting tumour-associated antigens directly to DCs in vivo is an alternative and simpler strategy. The identification of cell surface receptors on DCs, and targeting antigens to DC receptors, has become a popular approach for inducing effective immune responses against cancer antigens. Many years ago, we demonstrated that targeting the mannose receptor on macrophages using the carbohydrate mannan to DCs led to appropriate immune responses and tumour protection in animal models. We conducted Phase I, I/II and II, clinical trials demonstrating the effectiveness of oxidised mannan-MUC1 in patients with adenocarcinomas. Here we summarise DC targeting approaches and their efficacy in human clinical trials.

摘要

肿瘤相关抗原在癌症免疫治疗研究中的应用因对这些自身抗原的耐受而受到限制。通过使用体外单核细胞衍生的树突状细胞(DC)脉冲与自身抗原,可以打破耐受。将肿瘤相关抗原直接靶向体内的 DC 是一种替代且更简单的策略。鉴定 DC 表面受体,并将抗原靶向 DC 受体,已成为诱导针对癌症抗原的有效免疫反应的一种流行方法。多年前,我们证明了使用碳水化合物甘露聚糖将巨噬细胞上的甘露糖受体靶向 DC,可在动物模型中引发适当的免疫反应和肿瘤保护。我们进行了 I 期、I/II 期和 II 期临床试验,证明了氧化甘露聚糖-MUC1 在腺癌患者中的有效性。在这里,我们总结了 DC 靶向方法及其在人类临床试验中的疗效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/93bb/4232065/19ada4050126/cti201414f1.jpg

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