作为一种潜在的治疗方法,溶瘤病毒治疗既可作为单一治疗手段,也可与传统的化疗和放疗等手段相结合治疗肿瘤。本研究介绍了一个有效的,系统性的治疗方案,结合病毒治疗,通过过继免疫细胞治疗(ACT)技术(一种利用患者自身的肿瘤渗透性淋巴球的癌症治疗方式)发挥辅助免疫治疗作用。
研究者将ACT技术与全身性给予,表达内源性黑色素细胞抗原糖蛋白100(GP100)的水泡性口炎病毒(VSV)相结合。这种治疗方案使得黑色素瘤消退,并使机体产生抗肿瘤免疫。
肿瘤反应与体内T细胞的持续存在和激活以及治疗相关性白癜风密切相关。然而,在接受治疗的一部分小鼠中,最初的肿瘤消退往往伴随着以后的复发。为解决这一问题,研究者进一步针对一个额外的肿瘤抗原,结合之前的VSV-抗原与ACT相联合的策略,导致100%的受试小鼠持续发生治疗应答。
总之,该研究结果表明,系统性病毒治疗结合表达抗原的VSV的可以用来支持和加强,已经在临床上使用的过继免疫细胞治疗技术。(生物谷bioon.com)
doi:10.1016/j.cell.2011.10.017
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Systemic Combination Virotherapy For Melanoma With Tumor Antigen-Expressing Vesicular Stomatitis Virus And Adoptive T Cell Transfer
Diana Rommelfanger1,Phonphimon Wongthida1,Rosa M Diaz1,Karen M Kaluza1,Jill Thompson1,Timothy Kottke1, andRichard G Vile1
Oncolytic virotherapy offers the potential to treat tumors both as a single agent and in combination with traditional modalities such as chemotherapy and radiotherapy. Here we describe an effective, fully systemic treatment regimen, which combines virotherapy, acting essentially as an adjuvant immunotherapy, with adoptive cell transfer (ACT). The combination of ACT with systemic administration of a vesicular stomatitis virus (VSV) engineered to express the endogenous melanocyte antigen glycoprotein 100 (gp100) resulted in regression of established melanomas and generation of antitumor immunity. Tumor response was associated with in vivo T cell persistence and activation as well as treatment-related vitiligo. However, in a proportion of treated mice, initial tumor regressions were followed by recurrences. Therapy was further enhanced by targeting an additional tumor antigen with the VSV-antigen + ACT combination strategy, leading to sustained response in 100% of mice. Together, our findings suggest that systemic virotherapy combined with antigen-expressing VSV could be used to support and enhance clinical immunotherapy protocols with adoptive T cell transfer, which are already used in the clinic.