Grundy Erin E, Shaw Lauren C, Wang Loretta, Lee Abigail V, Argueta James Castro, Powell Daniel J, Ostrowski Mario, Jones R Brad, Cruz C Russell Y, Gordish-Dressman Heather, Chappell Nicole P, Bollard Catherine M, Chiappinelli Katherine B
Department of Microbiology, Immunology and Tropical Medicine, The George Washington University, Washington, DC, USA.
The George Washington University Cancer Center, Washington, DC, USA.
Mob DNA. 2024 Oct 9;15(1):19. doi: 10.1186/s13100-024-00333-w.
Transposable elements (TEs) 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 TE ERV-K is frequently expressed by tumor cells. Here we determined whether the targeting of previously identified epitope in the envelope gene (env) of ERV-K resulted in target antigen specificity against cancer cells. 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, in vitro priming of several healthy donors with this epitope of ERV-K-Env did not result in target antigen specificity. These data suggest that the T cell receptor is a poor candidate for targeting this specific ERV-K-Env epitope and has limited potential as a T cell therapy for OC.
转座元件（TEs）在肿瘤细胞中的表达水平通常高于正常细胞，这表明这些基因组区域是尚未开发的肿瘤相关抗原库。在卵巢癌（OC）中，肿瘤细胞经常表达来自TE ERV-K的蛋白质。在这里，我们确定靶向ERV-K包膜基因（env）中先前鉴定的表位是否会产生针对癌细胞的靶抗原特异性。我们发现，用ERV-K-Env特异性T细胞受体构建体转导健康供体T细胞，只有在与HLA-A*03:01 B淋巴母细胞共培养时才会产生抗原特异性。此外，用ERV-K-Env的这个表位对几个健康供体进行体外致敏并未产生靶抗原特异性。这些数据表明，T细胞受体不是靶向这个特定ERV-K-Env表位的理想选择，作为OC的T细胞疗法潜力有限。
