工程化益生菌用于肿瘤靶向联合化学免疫治疗
Engineered probiotics for tumor-targeted combination chemoimmunotherapy.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Harnessing the innate immune system by revolutionizing macrophage-mediated cancer immunotherapy.
Harnessing the innate immune system by revolutionizing macrophage-mediated cancer immunotherapy.
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免疫疗法是传统癌症疗法的一种有前景且更安全的替代方案。它涉及适应性T细胞疗法、癌症疫苗、单克隆抗体、免疫检查点阻断(ICB)以及基于嵌合抗原受体(CAR)的疗法。
然而,由于致密、高度缺氧和免疫抑制的微环境以及肿瘤抗原的异质性,大多数这些模式在实体瘤中遇到限制。快速生长的实体瘤内升高的瘤内压力和突变率对有效的药物靶向和递送提出了挑战。肿瘤微环境是一个动态的生态位,被多种免疫细胞浸润,其中大多数是巨噬细胞。由于它们构成先天免疫系统的一部分,靶向巨噬细胞已成为一种可行的免疫治疗方法。在这篇综述中,我们讨论了几种多功能的策略(包括临床前和临床阶段),例如直接杀死肿瘤相关巨噬细胞、将促肿瘤巨噬细胞重编程为抗肿瘤表型、抑制巨噬细胞募集到肿瘤微环境、新型CAR巨噬细胞以及迄今为止设计的基因工程化巨噬细胞。这些策略构成了在持续抗击癌症中强大且适应性强的巨噬细胞工具包,通过理解它们的重要性,我们可能释放这些免疫细胞在癌症治疗中的全部潜力。
Immunotherapy is a promising and safer alternative to conventional cancer therapies. It involves adaptive T-cell therapy, cancer vaccines, monoclonal antibodies, immune checkpoint blockade (ICB), and chimeric antigen receptor (CAR) based therapies.
However, most of these modalities encounter restrictions in solid tumours owing to a dense, highly hypoxic and immune-suppressive microenvironment as well as the heterogeneity of tumour antigens. The elevated intra-tumoural pressure and mutational rates within fastgrowing solid tumours present challenges in efficient drug targeting and delivery. The tumour microenvironment is a dynamic niche infiltrated by a variety of immune cells, most of which are macrophages. Since they form a part of the innate immune system, targeting macrophages has become a plausible immunotherapeutic approach.
In this review, we discuss several versatile approaches (both at pre-clinical and clinical stages) such as the direct killing of tumour-associated macrophages, reprogramming pro-tumour macrophages to anti-tumour phenotypes, inhibition of macrophage recruitment into the tumour microenvironment, novel CAR macrophages, and genetically engineered macrophages that have been devised thus far.
These strategies comprise a strong and adaptable macrophage-toolkit in the ongoing fight against cancer and by understanding their significance, we may unlock the full potential of these immune cells in cancer therapy.
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