Muvarak Nidal, Li Haishan, Lahusen Tyler, Galvin Jeffrey A, Kumar Princy N, Pauza C David, Bordon José
American Gene Technologies International, Inc., Rockville, MD, United States.
Georgetown University School of Medicine, Washington, DC, United States.
Front Med (Lausanne). 2022 Nov 14;9:1044713. doi: 10.3389/fmed.2022.1044713. eCollection 2022.
The cell and gene therapy product AGT103-T was designed to restore the Gag-specific CD4+ T cell response in persons with chronic HIV disease who are receiving antiretroviral therapy. This autologous, genetically engineered cell product is under investigation in a Phase 1 clinical trial (NCT03215004). Trial participants were conditioned with cyclophosphamide approximately 1 week before receiving a one-time low (< 10 genetically modified CD4+ T cells) or high (≥10 genetically modified CD4+ T cells) dose of AGT103-T, delivering between 2 and 21 million genetically modified cells per kilogram (kg) body weight. There were no serious adverse events (SAEs) and all adverse events (AEs) were mild. Genetically modified AGT103-T cells were detected in most of the participant blood samples collected 6 months after infusion, which was the last scheduled monitoring visit. Peripheral blood mononuclear cells (PBMC) collected after cell product infusion were tested to determine the abundance of Gag-specific T cells as a measure of objective responses to therapy. Gag-specific CD4+ T cells were detected in all treated individuals and were substantially increased by 9 to 300-fold compared to baseline, by 14 days after cell product infusion. Gag-specific CD8+ T cells were increased by 1.7 to 10-fold relative to baseline, by 28 days after cell product infusion. Levels of Gag-specific CD4+ T cells remained high (~2 to 70-fold higher relative to baseline) throughout 3-6 months after infusion. AGT103-T at low or high doses was safe and effective for improving host T cell immunity to HIV. Further studies, including antiretroviral treatment interruption, are warranted to evaluate the product's efficacy in HIV disease.
www.clinicaltrials.gov, identifier: NCT03215004.
细胞和基因治疗产品AGT103-T旨在恢复接受抗逆转录病毒治疗的慢性HIV疾病患者的Gag特异性CD4+ T细胞反应。这种自体基因工程细胞产品正在进行1期临床试验（NCT03215004）。试验参与者在接受一次性低剂量（<10个基因改造的CD4+ T细胞）或高剂量（≥10个基因改造的CD4+ T细胞）AGT103-T之前约1周接受环磷酰胺预处理，每公斤体重输送200万至2100万个基因改造细胞。未发生严重不良事件（SAE），所有不良事件（AE）均为轻度。在输注后6个月（即最后一次预定监测访视）采集的大多数参与者血液样本中检测到基因改造的AGT103-T细胞。对细胞产品输注后采集的外周血单核细胞（PBMC）进行检测，以确定Gag特异性T细胞的丰度，作为治疗客观反应的指标。在所有接受治疗的个体中均检测到Gag特异性CD4+ T细胞，与基线相比，在细胞产品输注后14天大幅增加了9至300倍。与基线相比，在细胞产品输注后28天，Gag特异性CD8+ T细胞增加了1.7至10倍。在输注后的3至6个月内，Gag特异性CD4+ T细胞水平一直保持较高（相对于基线高约2至70倍）。低剂量或高剂量的AGT103-T在改善宿主对HIV的T细胞免疫方面是安全有效的。有必要进行进一步研究，包括抗逆转录病毒治疗中断，以评估该产品在HIV疾病中的疗效。
