Chiocca E Antonio, Smith Katie M, McKinney Byron, Palmer Cheryl A, Rosenfeld Steven, Lillehei Kevin, Hamilton Allan, DeMasters Betty K, Judy Kevin, Kirn David
Department of Neurosurgery, Dardinger Neuro-oncology Center, James Comprehensive Cancer Center, The Ohio State University Medical Center, Columbus, Ohio, USA.
Biogen Idec Inc., San Diego, California, USA.
Mol Ther. 2008 Mar;16(3):618-626. doi: 10.1038/sj.mt.6300396. Epub 2016 Dec 8.
Interferon-β (IFN-β) is a pleiotropic cytokine with antitumoral activity. In an effort to improve the therapeutic index of IFN-β by providing local, sustained delivery of IFN-β to gliomas, the safety and biological activity of a human IFN-β (hIFN-β)-expressing adenovirus vector (Ad.hIFN-β) was evaluated in patients with malignant glioma by stereotactic injection, followed 4-8 days later by surgical removal of tumor with additional injections of Ad.hIFN-β into the tumor bed. Eleven patients received Ad.hIFN-β in cohorts of 2 × 10, 6 × 10, or 2 × 10 vector particles (vp). The most common adverse events were considered by the investigator as being unrelated to treatment. One patient, who was enrolled in the cohort with the highest dose levels, experienced dose-limiting, treatment-related Grade 4 confusion following the post-operative injection. Ad.hIFN-β DNA was detected within the tumor, blood, and nasal swabs in a dose-dependent fashion and hIFN-β protein was detectable within the tumor. At the highest doses tested, a reproducible increase in tumor cell apoptosis in post-treatment versus pre-treatment biopsies with associated tumor necrosis was observed. Direct Ad.hIFN-β injection into the tumor and the surrounding normal brain areas after surgical removal was feasible and associated with apoptosis induction.
干扰素-β（IFN-β）是一种具有抗肿瘤活性的多效性细胞因子。为了通过向胶质瘤局部持续递送IFN-β来提高IFN-β的治疗指数，通过立体定向注射在恶性胶质瘤患者中评估了表达人IFN-β（hIFN-β）的腺病毒载体（Ad.hIFN-β）的安全性和生物学活性，4至8天后通过手术切除肿瘤，并向瘤床额外注射Ad.hIFN-β。11名患者以2×10、6×10或2×10载体颗粒（vp）的剂量组接受Ad.hIFN-β。研究者认为最常见的不良事件与治疗无关。一名入组最高剂量组的患者在术后注射后出现了与治疗相关的剂量限制性4级意识模糊。在肿瘤、血液和鼻拭子中以剂量依赖性方式检测到Ad.hIFN-β DNA，并且在肿瘤中可检测到hIFN-β蛋白。在测试的最高剂量下，观察到与相关肿瘤坏死相关的治疗后与治疗前活检相比肿瘤细胞凋亡有可重复的增加。手术切除后将Ad.hIFN-β直接注射到肿瘤和周围正常脑区是可行的，并且与诱导凋亡有关。
