Zhen Anjie, Carrillo Mayra A, Kitchen Scott G
Division of Hematology & Oncology, Department of Medicine; UCLA AIDS Institute, David Geffen School of Medicine University of California, Los Angeles, CA 90095, USA.
Immunotherapy. 2017 Mar;9(5):401-410. doi: 10.2217/imt-2016-0121.
Despite the success of combination antiretroviral therapy (cART) for suppressing HIV and improving patients' quality of life, HIV persists in cART-treated patients and remains an incurable disease. Financial burdens and health consequences of lifelong cART treatment call for novel HIV therapies that result in a permanent cure. Cellular immunity is central in controlling HIV replication. However, HIV adopts numerous strategies to evade immune surveillance. Engineered immunity via genetic manipulation could offer a functional cure by generating cells that have enhanced antiviral activity and are resistant to HIV infection. Recently, encouraging reports from several human clinical trials using an anti-CD19 chimeric antigen receptor (CAR) modified T-cell therapy for treating B-cell malignancies have provided valuable insights and generated remarkable enthusiasm in engineered T-cell therapy. In this review, we discuss the development of HIV-specific chimeric antigen receptors and the use of stem cell based therapies to generate lifelong anti-HIV immunity.
尽管联合抗逆转录病毒疗法(cART)在抑制HIV和改善患者生活质量方面取得了成功,但HIV在接受cART治疗的患者体内仍然存在,并且该疾病仍然无法治愈。终身cART治疗带来的经济负担和健康后果促使人们寻求能够实现永久治愈的新型HIV疗法。细胞免疫在控制HIV复制中起着核心作用。然而,HIV采用多种策略来逃避免疫监视。通过基因操作进行的工程免疫可能通过产生具有增强抗病毒活性且对HIV感染具有抗性的细胞来实现功能性治愈。最近,几项使用抗CD19嵌合抗原受体(CAR)修饰的T细胞疗法治疗B细胞恶性肿瘤的人体临床试验的令人鼓舞的报告提供了有价值的见解,并在工程T细胞疗法领域引发了极大的热情。在这篇综述中,我们讨论了HIV特异性嵌合抗原受体的发展以及基于干细胞的疗法在产生终身抗HIV免疫力方面的应用。