CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Oncolytic Viruses as Reliable Adjuvants in CAR-T Cell Therapy for Solid Tumors.
Oncolytic Viruses as Reliable Adjuvants in CAR-T Cell Therapy for Solid Tumors.
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尽管最近在癌症治疗方面取得了具有影响力的科学进展,但未来仍有改进的机会。免疫疗法或许是最前沿的治疗类别之一,在临床环境中展现出潜力。基因工程T细胞表达嵌合抗原受体(CAR),能够识别癌细胞表面分子所表达的肿瘤相关抗原(TAA)信号。其有效性已在血液系统恶性肿瘤中得到广泛证实;因此,这些结果为其在广泛适应症中的应用奠定了基础。
然而,CAR-T 细胞技术在实体瘤中的应用面临若干挑战,例如免疫抑制性肿瘤微环境的存在和/或肿瘤浸润不足。因此,已有研究提出将CAR-T 细胞技术与其他方法联合使用。目前正在研究将CAR-T 细胞与溶瘤病毒疗法(使用经基因改造的病毒或天然存在的病毒)联合靶向肿瘤细胞的有效性,多项临床试验正在进行中。本叙述性综述总结了单独使用每种疗法及其联合应用方面的当前进展、机遇、优势与局限性。溶瘤病毒的使用为解决CAR-T 细胞疗法在尝试攻克实体瘤过程中所面临的现有挑战提供了机会,通过联合发挥各自优势来实现。
此外,利用溶瘤病毒使研究人员能够对病毒进行改造,从而实现特定治疗药物在肿瘤环境中的靶向递送。这反过来可能增强CAR-T 细胞技术对实体恶性肿瘤的细胞毒性效应和治疗潜力,在临床环境中产生具有影响力的结果。
Although impactful scientific advancements have recently been made in cancer therapy, there remains an opportunity for future improvements. Immunotherapy is perhaps one of the most cutting-edge categories of therapies demonstrating potential in the clinical setting.
Genetically engineered T cells express chimeric antigen receptors (CARs), which can detect signals expressed by the molecules present on the surface of cancer cells, also called tumor-associated antigens (TAAs). Their effectiveness has been extensively demonstrated in hematological cancers; therefore, these results can establish the groundwork for their applications on a wide range of requirements.
However, the application of CAR-T cell technology for solid tumors has several challenges, such as the existence of an immune-suppressing tumor microenvironment and/or inadequate tumor infiltration. Consequently, combining therapies such as CAR-T cell technology with other approaches has been proposed. The effectiveness of combining CAR-T cell with oncolytic virus therapy, with either genetically altered or naturally occurring viruses, to target tumor cells is currently under investigation, with several clinical trials being conducted.
This narrative review summarizes the current advancements, opportunities, benefits, and limitations in using each therapy alone and their combination. The use of oncolytic viruses offers an opportunity to address the existing challenges of CAR-T cell therapy, which appear in the process of trying to overcome solid tumors, through the combination of their strengths.
Additionally, utilizing oncolytic viruses allows researchers to modify the virus, thus enabling the targeted delivery of specific therapeutic agents within the tumor environment. This, in turn, can potentially enhance the cytotoxic effect and therapeutic potential of CAR-T cell technology on solid malignancies, with impactful results in the clinical setting.
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