Center for Cell and Gene Therapy, Baylor College of Medicine, The Methodist Hospital and Texas Children's Hospital, Houston, TX 77030, USA.
J Immunother. 2012 Feb-Mar;35(2):159-68. doi: 10.1097/CJI.0b013e318247642f.
Glioblastoma (GBM) is the most common primary brain cancer in adults and is virtually incurable. Recent studies have shown that cytomegalovirus (CMV) is present in majority of GBMs. To evaluate whether the CMV antigens pp65 and IE1, which are expressed in GBMs, could be targeted by CMV-specific T cells, we measured the frequency of T cells targeting pp65 and IE1 in the peripheral blood of a cohort of 11 sequentially diagnosed CMV-seropositive GBM patients, and evaluated whether it was feasible to expand autologous CMV-specific T cells for future clinical studies. All 11 CMV-seropositive GBM patients had T cells specific for pp65 and IE1 in their peripheral blood assessed by IFNγ enzyme-linked immunospot assay. However, the precursor frequency of pp65-specific T cells was decreased in comparison with healthy donors (P=0.001). We successfully reactivated and expanded CMV-specific T cells from 6 out of 6 GBM patients using antigen-presenting cells transduced with an adenoviral vector encoding pp65 and IE1. CMV-specific T-cell lines contained CD4 as well as CD8 T cells, recognized pp65 and IE1 targets and killed CMV-infected autologous GBM cells. Infusion of such CMV-specific T-cell lines may extend the benefits of T-cell therapy to patients with CMV GBMs.
胶质母细胞瘤（GBM）是成人中最常见的原发性脑癌，几乎无法治愈。最近的研究表明，巨细胞病毒（CMV）存在于大多数 GBM 中。为了评估在 GBM 中表达的 CMV 抗原 pp65 和 IE1 是否可以被 CMV 特异性 T 细胞靶向，我们测量了一组 11 例连续诊断为 CMV 血清阳性的 GBM 患者外周血中针对 pp65 和 IE1 的 T 细胞的频率，并评估了是否可以扩大自体 CMV 特异性 T 细胞用于未来的临床研究。通过 IFNγ酶联免疫斑点试验，所有 11 例 CMV 血清阳性 GBM 患者的外周血中均存在针对 pp65 和 IE1 的 T 细胞。然而，与健康供体相比，pp65 特异性 T 细胞的前体频率降低（P=0.001）。我们使用转导有编码 pp65 和 IE1 的腺病毒载体的抗原呈递细胞，成功地从 6 例 GBM 患者中重新激活和扩增了 CMV 特异性 T 细胞。CMV 特异性 T 细胞系含有 CD4 和 CD8 T 细胞，可识别 pp65 和 IE1 靶标，并杀死 CMV 感染的自体 GBM 细胞。输注这种 CMV 特异性 T 细胞系可能会将 T 细胞治疗的益处扩展到 CMV GBM 患者。
