Sharma Sandhya, Leung Wingchi K, Heslop Helen E
Center for Cell and Gene Therapy, Baylor College of Medicine, Houston Methodist Hospital and Texas Children's Hospital, Houston, Texas.
Interdepartmental Program in Translational Biology and Molecular Medicine, Baylor College of Medicine.
Curr Stem Cell Rep. 2020 Jun;6(2):17-29. doi: 10.1007/s40778-020-00170-6. Epub 2020 May 7.
Virus-associated malignancies are a global health burden, constituting 10-12% of cancers worldwide. As these tumors express foreign viral antigens that can elicit specific T cell responses, virus-directed immunotherapies are a promising treatment strategy. Specifically, adoptive cell transfer of virus-specific T cells (VSTs) has demonstrated the potential to eradicate cancers associated with certain viruses.
Initial studies in 1990s first showed that VSTs specific for the Epstein-Barr virus (EBVSTs) can induce complete remissions in patients with post-transplant lymphoproliferative disease. Since then, studies have validated the specificity and safety of VSTs in multiple lymphomas and solid malignancies. However, challenges remain to optimize this platform for widespread use, including enhancing potency and persistence, overcoming the immunosuppressive tumor microenvironment, and streamlining manufacturing processes that comply with regulatory requirements.
This review focuses on data from clinical trials evaluating VSTs directed against three viruses (EBV, HPV and MCPyV), as well as recent preclinical and clinical advances, and potential future directions.
病毒相关恶性肿瘤是一项全球健康负担，占全球癌症的10%-12%。由于这些肿瘤表达可引发特异性T细胞反应的外来病毒抗原，病毒导向免疫疗法是一种很有前景的治疗策略。具体而言，病毒特异性T细胞（VST）的过继性细胞转移已显示出根除某些病毒相关癌症的潜力。
20世纪90年代的初步研究首次表明，针对爱泼斯坦-巴尔病毒的VST（EBVST）可使移植后淋巴细胞增生性疾病患者完全缓解。从那时起，研究已证实VST在多种淋巴瘤和实体恶性肿瘤中的特异性和安全性。然而，要优化这个平台以供广泛使用仍存在挑战，包括提高效力和持久性、克服免疫抑制性肿瘤微环境以及简化符合监管要求的生产流程。
本综述重点关注评估针对三种病毒（EBV、HPV和MCPyV）的VST的临床试验数据，以及近期临床前和临床进展及潜在的未来方向。
