CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：Limited Immunogenicity of an HLA-A*03:01-restricted Epitope of Erv-k-env in Non-hiv-1 Settings: Implications for Adoptive Cell Therapy in Cancer.
Limited Immunogenicity of an HLA-A*03:01-restricted Epitope of Erv-k-env in Non-hiv-1 Settings: Implications for Adoptive Cell Therapy in Cancer.
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重复元件（REs）在肿瘤细胞中的表达水平通常高于正常细胞，这提示这些基因组区域是尚未被开发的肿瘤相关抗原库。在卵巢癌（OC）中，RE ERV-K 的蛋白常由肿瘤细胞表达。在此，我们确定了靶向 ERV-K 包膜基因（env）中先前已鉴定的免疫原性表位是否能在非 HIV-1 环境中产生靶抗原特异性。我们发现，用 ERV-K-Env 特异性 T 细胞受体构建体转导健康供者 T 细胞后，仅在与 HLA-A*03:01 B 淋巴母细胞样细胞共培养时才产生抗原特异性。此外，这些转导的 T 细胞对 HLA-A*03:01 + OC 细胞不具有特异性，在来自多个健康供者的 HLA 匹配系统中对该同源肽也不具有特异性。这些数据表明，该 T 细胞受体所识别的 ERV-K-Env 表位免疫原性较低，作为 OC 的 T 细胞靶点潜力有限。
Repetitive elements (REs) are often expressed at higher levels in tumor cells than normal cells, implicating these genomic regions as an untapped pool of tumor-associated antigens. In ovarian cancer (OC), protein from the RE ERV-K is frequently expressed by tumor cells.
Here we determined whether the targeting of a previously identified immunogenic epitope in the envelope gene (env) of ERV-K resulted in target antigen specificity in non-HIV-1 settings.
We found that transducing healthy donor T cells with an ERV-K-Env-specific T cell receptor construct resulted in antigen specificity only when co-cultured with HLA-A*03:01 B lymphoblastoid cells.
Furthermore, these transduced T cells were not specific for HLA-A*03:01 + OC cells nor for the cognate peptide in HLA-matched systems from multiple healthy donors. These data suggest that the ERV-K-Env epitope recognized by this T cell receptor is of low immunogenicity and has limited potential as a T cell target for OC.
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