CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Leveraging oncovirus-derived antigen against the viral malignancies in adoptive cell therapies.
Leveraging oncovirus-derived antigen against the viral malignancies in adoptive cell therapies.
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过继性细胞疗法(ACTs)已经彻底改变了肿瘤免疫治疗,促使人们探索其针对肿瘤病毒的应用。肿瘤病毒如人乳头瘤病毒(HPV)、乙型肝炎病毒(HBV)、丙型肝炎病毒(HCV)和EB病毒(EBV)通过直接或间接的致癌机制,对人类恶性肿瘤的发生贡献显著(12-25%)。这些病毒持续或潜伏感染细胞,破坏细胞稳态和信号通路,对当前抗病毒治疗范式构成挑战。此外,在长期肿瘤治疗背景下,病毒感染带来额外风险,并导致发病率和死亡率。病毒编码的癌蛋白具有肿瘤限制性、免疫外来性,甚至均匀表达,代表了患者定制ACTs的有前景靶点。本综述阐明了利用病毒抗原特异性ACTs对抗病毒相关恶性肿瘤的理论依据。在此基础上,正在进行的临床前研究巩固了我们对利用ACTs对抗病毒性恶性肿瘤的理解,强调了其根除与癌症进展相关病毒的潜力。此外,我们审视了聚焦于病毒特异性ACTs的当前临床试验格局,并讨论了其对治疗进展的意义。
Adoptive cell therapies (ACTs) have revolutionized cancer immunotherapy, prompting exploration into their application against oncoviruses. Oncoviruses such as human papillomavirus (HPV), hepatitis B virus (HBV), hepatitis C virus (HCV), and Epstein-Barr virus (EBV) contribute significantly (12-25%) to human malignancies through direct or indirect oncogenic mechanisms. These viruses persistently or latently infect cells, disrupt cellular homeostasis and pathways, challenging current antiviral treatment paradigms.
Moreover, viral infections pose additional risks in the setting of long-term cancer therapy and lead to morbidity and mortality. Virally encoded oncoproteins, which are tumor-restricted, immunologically foreign, and even uniformly expressed, represent promising targets for patient-tailored ACTs.
This review elucidates the rationale for leveraging viral antigen-specific ACTs in combating viral-associated malignancies. On this basis, ongoing preclinical studies consolidate our understanding of harnessing ACTs against viral malignancies, underscoring their potential to eradicate viruses implicated in cancer progression.
Furthermore, we scrutinize the current landscape of clinical trials focusing on virus-specific ACTs and discuss their implications for therapeutic advancement.
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