PDF(Pubmed)
Abstract：
Cytokines are small proteins that regulate the growth and functional activity of immune cells, and several have been approved for cancer therapy. Oncolytic viruses are agents that mediate antitumor activity by directly killing tumor cells and inducing immune responses. Talimogene laherparepvec is an oncolytic herpes simplex virus type 1 (oHSV), approved for the treatment of recurrent melanoma, and the virus encodes the human cytokine, granulocyte-macrophage colony-stimulating factor (GM-CSF). A significant advantage of oncolytic viruses is the ability to deliver therapeutic payloads to the tumor site that can help drive antitumor immunity. While cytokines are especially interesting as payloads, the optimal cytokine(s) used in oncolytic viruses remains controversial. In this review, we highlight preliminary data with several cytokines and chemokines, including GM-CSF, interleukin 12, FMS-like tyrosine kinase 3 ligand, tumor necrosis factor α, interleukin 2, interleukin 15, interleukin 18, chemokine (C-C motif) ligand 2, chemokine (C-C motif) ligand 5, chemokine (C-X-C motif) ligand 4, or their combinations, and show how these payloads can further enhance the antitumor immunity of oHSV. A better understanding of cytokine delivery by oHSV can help improve clinical benefit from oncolytic virus immunotherapy in patients with cancer.
摘要：
细胞因子是调节免疫细胞生长和功能活性的小蛋白,和一些已被批准用于癌症治疗。溶瘤病毒是通过直接杀死肿瘤细胞和诱导免疫应答来介导抗肿瘤活性的试剂。Talimogenelaherparepvec是一种溶瘤性单纯疱疹病毒1型（oHSV），被批准用于治疗复发性黑色素瘤，病毒编码人类细胞因子，粒细胞-巨噬细胞集落刺激因子（GM-CSF）。溶瘤病毒的一个显著优点是能够将治疗性有效载荷递送到肿瘤部位,其可以帮助驱动抗肿瘤免疫。虽然细胞因子作为有效载荷特别有趣，溶瘤病毒中使用的最佳细胞因子仍存在争议.在这次审查中,我们强调了几种细胞因子和趋化因子的初步数据，包括GM-CSF,白细胞介素12，FMS样酪氨酸激酶3配体，肿瘤坏死因子α,白介素2，白介素15，白介素18，趋化因子（C-C基序）配体2，趋化因子（C-C基序）配体5，趋化因子（C-X-C基序）配体4或其组合，并显示这些有效载荷如何进一步增强oHSV的抗肿瘤免疫力。更好地了解oHSV的细胞因子递送可以帮助提高癌症患者溶瘤病毒免疫疗法的临床益处。
