决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Integrating CAR-T cells with other immunotherapies for improved efficacy in cancer patients.
嵌合抗原受体(CAR)T细胞疗法是一种新颖且创新的癌症治疗方法,尤其适用于血液癌症患者。
嵌合抗原受体(CAR)T细胞疗法是一种针对癌症患者,尤其是血液癌症患者的新型创新治疗方法。然而,实体瘤仍然是该疗法效果不佳的领域。面临的挑战包括抗原异质性、免疫抑制性肿瘤微环境以及一些尚未解决的严重副作用。本研究详细阐述了如何将不同的免疫治疗方法相互协同使用,以增强CAR-T细胞疗法的疗效并减少其作为单一疗法的局限性。我们的综述探讨了免疫检查点抑制剂(ICIs)、基于细胞因子的方法、造血干细胞移植(HSCT)、癌症疫苗、溶瘤病毒、单克隆抗体、NK细胞疗法、TIL(肿瘤浸润淋巴细胞)、双特异性T细胞衔接器(BiTEs)以及溶瘤病毒(OVs)如何与CAR-T细胞疗法联合使用。减少抑制性细胞群体和改善抗原呈递有助于OVs改造TME,使CAR-T细胞能够更好地渗透和持久存在。与此类似,BiTEs通过增加靶向抗原的细胞数量并引入旁观者T细胞,来解决抗原丢失和复发的问题。此外,细胞因子共递送和细胞内改变在降低全身毒性和增强CAR-T持续激活方面显示出前景。早期临床试验和临床前研究表明,这些联合策略可能有效,但仍存在剂量依赖性毒性、精确治疗时机和递送限制等问题。本综述总体强调了联合技术大幅提高CAR-T细胞治疗疗效和安全性的可能性,从而为癌症免疫治疗的后续研究和临床应用提供有见地的信息。
Chimeric Antigen Receptor (CAR) T cell therapy is a novel cum innovative treatment for cancer patients, especially the ones dealing with blood cancers. However, solid tumours remain an area where this therapy is not so effective. The challenges are antigen heterogeneity, immunosuppressive tumour microenvironment, and some unaddressed serious side effects. This study details how different immunotherapeutic approaches can be used in synergy with each other to augment efficacy of CAR-T cell-based therapy and to minimize its limitations as a standalone therapy. Our review looks at how immune checkpoint inhibitors (ICIs), cytokine-based approaches, hematopoietic stem cell transplantation (HSCT), cancer vaccines, oncolytic viruses, monoclonal antibodies, NK cell therapy, tumour-infiltrating lymphocytes, bispecific T-cell engagers (BiTEs), and oncolytic viruses (OVs) could be utilized together with CAR-T cell therapy. Reducing repressive cell populations and improving antigen presentation helps OVs modify the TME, enabling better CAR-T cell penetration and persistence. Similar to this, BiTEs deal with issues of antigen loss and relapse by increasing the number of cells that target antigens and bringing in bystander T-cells. Moreover, cytokine co-delivery and changes inside cells show promise in lowering systemic toxicity and increasing continuous CAR-T activation. Early-stage clinical trials and preclinical studies show that these combinatorial strategies may work, but there are still issues like dose-dependent toxicity, exact treatment timing, and delivery restrictions. This review highlights generally the possibilities of combinational techniques to greatly increase the efficacy and safety profile of CAR-T cell treatments, thus providing insightful information for next studies and clinical uses in cancer immunotherapy.
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