Treatment and Research Center for Infectious Diseases, The Fifth Medical Center, PLA General Hospital, Beijing, China.
Department of Hematology and Transplantation, The Fifth Medical Center, PLA General Hospital, Beijing, China.
Signal Transduct Target Ther. 2021 May 7;6(1):174. doi: 10.1038/s41392-021-00550-2.
Severely immunosuppressed AIDS patients with recurrent opportunistic infections (OIs) represent an unmet medical need even in the era of antiretroviral therapy (ART). Here we report the development of a human leukocyte antigen (HLA)-mismatched allogeneic adaptive immune therapy (AAIT) for severely immunosuppressed AIDS patients. Twelve severely immunosuppressed AIDS patients with severe OIs were enrolled in this single-arm study. Qualified donors received subcutaneous recombinant granulocyte-colony-stimulating factor twice daily for 4-5 days to stimulate hematopoiesis. Peripheral blood mononuclear cells were collected from these donors via leukapheresis and transfused into the coupled patients. Clinical, immunological, and virological parameters were monitored during a 12-month follow-up period. We found AAIT combined with ART was safe and well-tolerated at the examined doses and transfusion regimen in all 12 patients. Improvements in clinical symptoms were evident throughout the study period. All patients exhibited a steady increase of peripheral CD4 T cells from a median 10.5 to 207.5 cells/μl. Rapid increase in peripheral CD8 T-cell count from a median 416.5 to 1206.5 cells/μl was found in the first 90 days since initiation of AAIT. In addition, their inflammatory cytokine levels and HIV RNA viral load decreased. A short-term microchimerism with donor cells was found. There were no adverse events associated with graft-versus-host disease throughout the study period. Overall, AAIT treatment was safe, and might help severely immunosuppressed AIDS patients to achieve a better immune restoration. A further clinical trial with control is necessary to confirm the efficacy of AAIT medication.
严重免疫抑制的艾滋病患者（AIDS）反复发生机会性感染（OIs），即使在抗逆转录病毒治疗（ART）时代，也代表着尚未满足的医疗需求。在此，我们报告了一种用于严重免疫抑制 AIDS 患者的人类白细胞抗原（HLA）错配同种异体适应性免疫治疗（AAIT）的开发。这项单臂研究共纳入了 12 名严重免疫抑制、伴有严重 OIs 的 AIDS 患者。合格的供者接受皮下重组粒细胞集落刺激因子（G-CSF），每天 2 次，连续 4-5 天，以刺激造血。通过白细胞分离术从这些供者中采集外周血单个核细胞（PBMC），并输注给配对患者。在 12 个月的随访期间，监测临床、免疫和病毒学参数。我们发现，在研究中检查的剂量和输血方案下，AAIT 联合 ART 在所有 12 名患者中是安全且耐受良好的。整个研究期间，临床症状均有改善。所有患者的外周血 CD4 T 细胞均从中位数 10.5 增加至 207.5 个/μl。在开始 AAIT 的前 90 天内，外周血 CD8 T 细胞计数从中位数 416.5 增加至 1206.5 个/μl，迅速增加。此外，他们的炎症细胞因子水平和 HIV RNA 病毒载量降低。发现供者细胞的短期微嵌合体。整个研究期间，未发现与移植物抗宿主病相关的不良事件。总的来说，AAIT 治疗是安全的，可能有助于严重免疫抑制的 AIDS 患者实现更好的免疫恢复。需要进一步的对照临床试验来证实 AAIT 药物的疗效。
