Harrington Kevin J, Puzanov Igor, Hecht J Randolph, Hodi F Stephen, Szabo Zsolt, Murugappan Swami, Kaufman Howard L
a Division of Hematology-Oncology, Vanderbilt University Medical Center , Nashville , TN , USA.
b David Geffen School of Medicine , UCLA , Los Angeles , CA , USA.
Expert Rev Anticancer Ther. 2015;15(12):1389-403. doi: 10.1586/14737140.2015.1115725.
Tumor immunotherapy is emerging as a promising new treatment option for patients with cancer. T-VEC is an intralesional oncolytic virus therapy based on a modified herpes simplex virus type-1. T-VEC selectively targets tumor cells, causing regression in injected lesions and inducing immunologic responses that mediate regression at uninjected/distant sites. In a randomized phase III trial, T-VEC met its primary endpoint of improving the durable response rate vs granulocyte-macrophage colony-stimulating factor in patients with unresectable melanoma. Responses were observed in injected and uninjected regional and visceral lesions. Exploratory analyses suggested survival differences in favor of T-VEC in patients with untreated or stage IIIB/IIIC/IVM1a disease. T-VEC was generally well tolerated, the most common adverse events being flu-like symptoms. Here, we overview recent advances in cancer immunotherapy, focusing on the clinical development of T-VEC, from first-in-human studies and studies in other cancer types, to ongoing combination trials with checkpoint inhibitors.
肿瘤免疫疗法正成为一种有前景的癌症新治疗选择。T-VEC是一种基于改良1型单纯疱疹病毒的瘤内溶瘤病毒疗法。T-VEC选择性靶向肿瘤细胞，使注射部位的病灶缩小，并诱导免疫反应，介导未注射/远处部位的病灶缩小。在一项随机III期试验中，T-VEC达到了其主要终点，即在不可切除黑色素瘤患者中，与粒细胞-巨噬细胞集落刺激因子相比，提高了持久缓解率。在注射和未注射的局部及内脏病灶中均观察到缓解。探索性分析表明，在未治疗或IIIB/IIIC/IVM1a期疾病患者中，T-VEC组的生存情况更优。T-VEC总体耐受性良好，最常见的不良事件为流感样症状。在此，我们概述癌症免疫疗法的最新进展，重点关注T-VEC的临床开发，从首次人体研究及其他癌症类型的研究，到目前正在进行的与检查点抑制剂的联合试验。
