Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, California, USA; Torrey Pines Institute for Molecular Studies, San Diego, California, USA; ImmunoCellular Therapeutics, Ltd., Calabasas, Calfornia, USA.
Stem Cells Transl Med. 2014 Mar;3(3):356-64. doi: 10.5966/sctm.2013-0135. Epub 2013 Dec 27.
Targeting cancer stem cells (CSCs) with immunotherapy may be an effective means to prevent recurrences in glioblastoma multiforme (GBM). It is well established that CD133 is expressed in the population of GBM tumor cells representing CSCs. This raises a possibility that CD133 could serve as a potential target for cytotoxic T cells (CTLs) to target glioblastoma cancer stem cells. Two potential human leukocyte antigen (HLA)-A0201-restricted CD133 epitopes, ILSAFSVYV (CD133-405) and YLQWIEFSI (CD133-753), showed strong binding to HLA-A0201 molecules. In vitro immunogenicity studies generated peptide-specific CD8(+) CTLs from normal donors. Autologous monocyte-derived dendritic cells pulsed with the CD133-405 or CD133-753 peptides generated CTLs that efficiently recognized the CD133 epitopes presented in T2 HLA-A0201 cells and specifically lysed CD133+ HLA-A0201(+) GBM CSCs. These studies demonstrated natural processing and subsequent presentation of these epitopes in GBM CSCs and the ability of CTLs to kill CSCs bearing the antigen. Immunization studies in mice using the mouse homolog CD133 epitopes demonstrated immunogenicity in the absence of autoimmune damage. The results presented in this study support the use of CD133-specific epitope vaccines to target CSCs in glioblastoma and other cancers.
针对癌症干细胞（CSCs）的免疫疗法可能是预防多形性胶质母细胞瘤（GBM）复发的有效手段。已有研究证实，CD133 在代表 CSCs 的 GBM 肿瘤细胞群体中表达。这就提出了一种可能性，即 CD133 可以作为细胞毒性 T 细胞（CTL）靶向神经胶质瘤癌症干细胞的潜在靶标。两个潜在的人类白细胞抗原（HLA）-A0201 限制性 CD133 表位，ILSAFSVYV（CD133-405）和 YLQWIEFSI（CD133-753），与 HLA-A0201 分子具有强烈的结合能力。体外免疫原性研究从正常供体中产生了针对肽的 CD8+CTL。用 CD133-405 或 CD133-753 肽脉冲处理的自体单核细胞衍生树突状细胞产生的 CTL 能够有效地识别在 T2 HLA-A0201 细胞中呈递的 CD133 表位，并特异性裂解 CD133+HLA-A0201+GBM CSCs。这些研究表明这些表位在 GBM CSCs 中存在天然加工和随后的呈递，以及 CTL 杀伤携带抗原的 CSCs 的能力。使用鼠同源 CD133 表位在小鼠中的免疫研究表明在没有自身免疫损伤的情况下具有免疫原性。本研究的结果支持使用 CD133 特异性表位疫苗来靶向神经胶质瘤和其他癌症中的 CSCs。
