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:Adoptive cell therapy in paediatric extracranial solid tumours: current approaches and future challenges.
Adoptive cell therapy in paediatric extracranial solid tumours: current approaches and future challenges.
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免疫治疗为传统疗法难治的儿童实体瘤带来了治愈希望,其中最有前景的方法之一是过继细胞治疗(ACT)。尤其是采用嵌合抗原受体(CAR)改造T细胞的ACT,已成为临床研究焦点。然而,ACT疗效受到细胞治疗内在因素(如活化不足或T细胞耗竭)以及儿童实体瘤免疫逃逸策略(如高度免疫抑制性微环境)的限制。为克服这些挑战,研究人员正在开发新策略,包括采用先天样淋巴细胞的ACT、新型细胞工程技术及ACT联合疗法。本文讨论儿童颅外实体瘤治疗中ACT的主要类别,综述支持有前景策略的临床前及临床证据,并探讨ACT仍面临的挑战。最后,本文重点介绍当前先进进展及新治疗选择的机会,这些发展有望改善这一治疗棘手人群的结局。
Immunotherapy has ignited hope to cure paediatric solid tumours that resist traditional therapies. Among the most promising methods is adoptive cell therapy (ACT). Particularly, ACT using T cells equipped with chimeric antigen receptors (CARs) has moved into the spotlight in clinical studies.
However, the efficacy of ACT is challenged by ACT-intrinsic factors, like lack of activation or T cell exhaustion, as well as immune evasion strategies of paediatric solid tumours, such as their highly immunosuppressive microenvironment. Novel strategies, including ACT using innate-like lymphocytes, innovative cell engineering techniques, and ACT combination therapies, are being developed and will be crucial to overcome these challenges.
Here, we discuss the main classes of ACT for the treatment of paediatric extracranial solid tumours, reflect on the available preclinical and clinical evidence supporting promising strategies, and address the challenges that ACT is still facing. Ultimately, we highlight state-of-the-art developments and opportunities for new therapeutic options, which hold great potential for improving outcomes in this challenging patient population.
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