Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA , 19104, USA.
Cytotechnology. 2004 Jun;45(1-2):91-9. doi: 10.1007/s10616-004-5132-2.
Telomerase reverse transcriptase hTERT is an attractive target for cancer immunotherapy given its broad expression in human tumors and its demonstrated immunogenicity. Human and murine model systems demonstrate that CD8(+) cytotoxic T-lymphocytes (CTL) and CD4(+) helper T-lymphocytes can recognize dominant epitopes derived from TERT. CTL kill TERT-positive tumor cells of multiple histologies, although there is some disagreement regarding the level of processing and presentation of certain TERT peptides within the context of MHC class I molecules. CTL recognizing modified, low-affinity cryptic TERT epitopes have also been generated that protect against tumor challenge in a murine model. Several phase I clinical trials testing hTERT as a cancer vaccine target have shown the induction of T-cell immune responses but minimal toxicities, including bone marrow toxicity, in patients with multiple types of cancer. Several studies report some patients experiencing clinical benefit, including partial tumor regression, providing further encouragement for hTERT as broadly applicable target for cancer immunotherapy.
端粒酶逆转录酶 hTERT 因其在人类肿瘤中的广泛表达及其免疫原性已成为癌症免疫治疗的一个有吸引力的靶点。人和鼠模型系统表明，CD8+细胞毒性 T 淋巴细胞（CTL）和 CD4+辅助 T 淋巴细胞可以识别源自 TERT 的优势表位。CTL 可杀死多种组织学类型的 TERT 阳性肿瘤细胞，尽管在 MHC Ⅰ类分子的背景下，某些 TERT 肽的加工和呈递水平存在一些争议。CTL 还可以识别经过修饰的低亲和力隐匿 TERT 表位，这些表位可以在鼠模型中预防肿瘤挑战。几项测试 hTERT 作为癌症疫苗靶点的 I 期临床试验表明，在多种癌症患者中诱导了 T 细胞免疫反应，但毒性最小，包括骨髓毒性。几项研究报告称，一些患者出现了临床获益，包括部分肿瘤消退，这为 hTERT 作为广泛适用的癌症免疫治疗靶点提供了进一步的鼓励。
