School of Medicine, Duke University, Durham, NC 27710, USA.
Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
Front Biosci (Landmark Ed). 2022 Feb 14;27(2):63. doi: 10.31083/j.fbl2702063.
Malignant melanoma recurrence remains heterogeneous in presentation, ranging from locoregional disease (i.e., local recurrence, satellites, in transit disease) to distant dermal and visceral metastases. This diverse spectrum of disease requires a personalized approach to management and has resulted in the development of both local (e.g., surgery, radiation, intralesional injection) and systemic (intravenous or oral) treatment strategies. Intralesional agents such as oncolytic viruses may also evoke local immune stimulation to induce and enhance the antitumor immune response. Further, it is hypothesized that these oncolytic viruses may convert immunologically "cold" tumors to more reactive "hot" tumor microenvironments and thereby overcome anti-PD-1 therapy resistance. Currently, talimogene laherparepvec (T-VEC), a modified herpes virus, is FDA-approved in this population, with many other oncolytic viruses under investigation in both preclinical and trial settings. Herein, we detail the scientific rationale, current landscape, and future directions of oncolytic viruses in melanoma.
恶性黑色素瘤的复发表现存在异质性,包括局部疾病(即局部复发、卫星灶、播散性疾病)和远处皮肤和内脏转移。这种多样化的疾病谱需要个性化的管理方法,因此开发了局部(如手术、放疗、局部注射)和全身(静脉或口服)治疗策略。局部药物如溶瘤病毒也可以引发局部免疫刺激,从而诱导和增强抗肿瘤免疫反应。此外,人们假设这些溶瘤病毒可以将免疫上“冷”的肿瘤转化为更具反应性的“热”肿瘤微环境,从而克服抗 PD-1 治疗的耐药性。目前,一种经过改良的疱疹病毒 talimogene laherparepvec(T-VEC)已获 FDA 批准用于该人群,许多其他溶瘤病毒正在临床前和临床试验中进行研究。本文详细介绍了溶瘤病毒在黑色素瘤中的科学原理、现状和未来方向。