Grigg Claud, Blake Zoë, Gartrell Robyn, Sacher Adrian, Taback Bret, Saenger Yvonne
Hematology/Oncology, New York-Presbyterian/Columbia University Medical Center, New York, NY.
Hematology/Oncology, Columbia University Medical Center, New York, NY.
Semin Oncol. 2016 Dec;43(6):638-646. doi: 10.1053/j.seminoncol.2016.10.005. Epub 2016 Oct 27.
Talimogene laherparepvec (T-Vec) is the first live virus to be approved by the US Food and Drug Administration for the treatment of cancer. This engineered version of herpes simplex virus type 1 (HSV-1) is the product of decades of preclinical work aimed at identifying and modifying aspects of the viral genome involved in virulence and immunogenicity. T-Vec preferentially infects and lyses tumor cells and, in some cases, induces a systemic immune response against the tumor. These properties have translated into significant and durable clinical responses, particularly in advanced melanoma. Many unanswered questions remain, including how to augment these clinical responses and which other tumor types may respond to oncolytic therapy. Here, we review the development of T-Vec, our current understanding of its impact on the tumor immune micro-environment, and its safety and efficacy in clinical trials for melanoma and other cancers.
Talimogene laherparepvec(T-Vec)是首个获美国食品药品监督管理局批准用于治疗癌症的活病毒。这种经过基因工程改造的1型单纯疱疹病毒(HSV-1)是数十年临床前研究工作的成果,旨在识别和修改病毒基因组中与毒力和免疫原性相关的方面。T-Vec优先感染并裂解肿瘤细胞,在某些情况下,还会引发针对肿瘤的全身性免疫反应。这些特性已转化为显著且持久的临床反应,尤其是在晚期黑色素瘤中。仍有许多未解决的问题,包括如何增强这些临床反应以及哪些其他肿瘤类型可能对溶瘤疗法有反应。在此,我们回顾T-Vec的研发历程、我们目前对其对肿瘤免疫微环境影响的理解,以及其在黑色素瘤和其他癌症临床试验中的安全性和疗效。