Sohai Danielle K, Keller Michael D, Hanley Patrick J, Hoq Fahmida, Kukadiya Divyesh, Datar Anushree, Reynolds Emily, Copertino Dennis C, Lazarski Christopher, McCann Chase D, Tanna Jay, Shibli Abeer, Lang Haili, Zhang Anqing, Chansky Pamela A, Motta Cecilia, Huynh Tan T, Dwyer Bridget, Wilson Andrew, Lynch Rebecca, Mota Talia M, Conce Alberto Winiffer D, Brumme Zabrina L, Kinloch Natalie N, Cruz Conrad Russell Y, MacLaren Ehui Lynsay, Henn Sarah, Brad Jones R, Bollard Catherine M
Center for Cancer and Immunology Research, and Division of Biostatistics and Study Methodology, Children's National Hospital, Washington, DC, USA.
Integrated Biomedical Sciences, Department of Microbiology, Immunology, and Tropical Medicine, and Department of Pediatrics, The George Washington University, Washington, DC, USA.
Nat Commun. 2025 May 15;16(1):4510. doi: 10.1038/s41467-025-59810-2.
Novel cellular therapies may enable HIV control or cure. HIV-specific T cells targeting conserved immunogenic protein regions of HIV Gag/Pol and the entirety of HIV Nef, termed HST-NEETs, eliminate HIV infected cells in vitro. Here we enroll seven participants in an open-label, single-arm phase 1 study (NCT03485963) to evaluate the safety (primary endpoint) of two autologous administrations of HST-NEET products without prescribed lymphodepletion. Adults with well-controlled HIV on anti-retroviral therapy are eligible. Six participants completed safety monitoring. No serious product-related toxicities are observed. Secondary endpoints are to assess expansion and persistence of HIV-reactive T cell clones, and changes to the HIV reservoir for each infused participant. HIV-specific T cell and HIV anti-Env antibody responses increase in two participants after infusion two. A trend towards decreasing levels of intact proviruses is observed in 2 participants. Three participants show persistence of HIV-reactive, product-associated T cell clones for ≥40 weeks post infusions. HST-NEETs infusions are well-tolerated. Future trials are needed to evaluate the efficacy of HST-NEETs in this population.
新型细胞疗法或许能够实现对HIV的控制或治愈。靶向HIV Gag/Pol保守免疫原性蛋白区域以及整个HIV Nef的HIV特异性T细胞，即HST-NEETs，可在体外清除HIV感染细胞。在此，我们招募了7名参与者，开展一项开放标签、单臂1期研究（NCT03485963），以评估在未进行预定淋巴细胞清除的情况下两次自体注射HST-NEET产品的安全性（主要终点）。接受抗逆转录病毒疗法且HIV病情得到良好控制的成年人均符合条件。6名参与者完成了安全性监测。未观察到与产品相关的严重毒性反应。次要终点是评估HIV反应性T细胞克隆的扩增和持久性，以及每位输注参与者HIV储存库的变化。在第二次输注后，两名参与者的HIV特异性T细胞和HIV抗Env抗体反应增强。2名参与者出现完整前病毒水平下降的趋势。3名参与者在输注后≥40周显示出HIV反应性、与产品相关的T细胞克隆持续存在。HST-NEETs输注耐受性良好。未来需要开展试验来评估HST-NEETs在该人群中的疗效。
