Ferrari Guido, Haynes Barton F, Koenig Scott, Nordstrom Jeffrey L, Margolis David M, Tomaras Georgia D
Department of Surgery, Duke University, Durham, North Carolina 27710, USA.
Department of Molecular Genetics and Microbiology, Duke University, Durham, North Carolina 27710, USA.
Nat Rev Drug Discov. 2016 Dec;15(12):823-834. doi: 10.1038/nrd.2016.173. Epub 2016 Oct 7.
HIV-1 is a retrovirus that integrates into host chromatin and can remain transcriptionally quiescent in a pool of immune cells. This characteristic enables HIV-1 to evade both host immune responses and antiretroviral drugs, leading to persistent infection. Upon reactivation of proviral gene expression, HIV-1 envelope (HIV-1 Env) glycoproteins are expressed on the cell surface, transforming latently infected cells into targets for HIV-1 Env-specific monoclonal antibodies (mAbs), which can engage immune effector cells to kill productively infected CD4 T cells and thus limit the spread of progeny virus. Recent innovations in antibody engineering have resulted in novel immunotherapeutics such as bispecific dual-affinity re-targeting (DART) molecules and other bi- and trispecific antibody designs that can recognize HIV-1 Env and recruit cytotoxic effector cells to kill CD4 T cells latently infected with HIV-1. Here, we review these immunotherapies, which are designed with the goal of curing HIV-1 infection.
HIV-1是一种逆转录病毒，可整合到宿主染色质中，并能在一群免疫细胞中保持转录静止状态。这一特性使HIV-1能够逃避宿主免疫反应和抗逆转录病毒药物，从而导致持续性感染。一旦前病毒基因表达重新激活，HIV-1包膜（HIV-1 Env）糖蛋白就会在细胞表面表达，将潜伏感染的细胞转变为HIV-1 Env特异性单克隆抗体（mAb）的靶标，这些抗体可促使免疫效应细胞杀死高效感染的CD4 T细胞，从而限制子代病毒的传播。抗体工程领域的最新创新成果带来了新型免疫疗法，如双特异性双亲和力重定向（DART）分子以及其他双特异性和三特异性抗体设计，它们能够识别HIV-1 Env并募集细胞毒性效应细胞来杀死潜伏感染HIV-1的CD4 T细胞。在此，我们综述这些旨在治愈HIV-1感染的免疫疗法。
