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基于基因工程化巨噬细胞的癌症免疫疗法。

Cancer Immunotherapies Based on Genetically Engineered Macrophages.

机构信息

École normale supérieure de Lyon, Département de biologie, Master biologie, Lyon, France.

Institut Curie, PSL University, Inserm U932, Immunity and Cancer, Paris, France.

出版信息

Cancer Immunol Res. 2022 Oct 4;10(10):1156-1166. doi: 10.1158/2326-6066.CIR-22-0030.

Abstract

Anticancer immunotherapies are therapeutics aimed at eliciting immune responses against tumor cells. Immunotherapies based on adoptive transfer of engineered immune cells have raised great hopes of cures because of the success of chimeric antigen receptor T-cell therapy in treating some hematologic malignancies. In parallel, advances in detailed analyses of the microenvironment of many solid tumors using high-dimensional approaches have established the origins and abundant presence of tumor-associated macrophages. These macrophages have an anti-inflammatory phenotype and promote tumor growth through a variety of mechanisms. Attempts have been made to engineer macrophages with chimeric receptors or transgenes to counteract their protumor activities and promote their antitumor functions such as phagocytosis of cancer cells, presentation of tumor antigens, and production of inflammatory cytokines. In this review, we cover current breakthroughs in engineering myeloid cells to combat cancer as well as potential prospects for myeloid-cell treatments.

摘要

抗癌免疫疗法是旨在引发针对肿瘤细胞的免疫反应的疗法。基于过继转移工程化免疫细胞的免疫疗法,由于嵌合抗原受体 T 细胞疗法在治疗某些血液恶性肿瘤方面的成功,带来了治愈的巨大希望。与此同时,使用高维方法对许多实体瘤的微环境进行详细分析的进展,确立了肿瘤相关巨噬细胞的起源和丰富存在。这些巨噬细胞具有抗炎表型,并通过多种机制促进肿瘤生长。人们试图用嵌合受体或转基因工程改造巨噬细胞,以抵消其促肿瘤活性,并促进其抗肿瘤功能,如吞噬癌细胞、呈递肿瘤抗原和产生炎症细胞因子。在这篇综述中,我们介绍了当前用于对抗癌症的髓系细胞工程学的突破,以及髓系细胞治疗的潜在前景。

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