作為一種潛在的治療方法,,溶瘤病毒治療既可作為單一治療手段,也可與傳統(tǒng)的化療和放療等手段相結(jié)合治療腫瘤,。本研究介紹了一個(gè)有效的,,系統(tǒng)性的治療方案,結(jié)合病毒治療,,通過(guò)過(guò)繼免疫細(xì)胞治療(ACT)技術(shù)(一種利用患者自身的腫瘤滲透性淋巴球的癌癥治療方式)發(fā)揮輔助免疫治療作用,。
研究者將ACT技術(shù)與全身性給予,表達(dá)內(nèi)源性黑色素細(xì)胞抗原糖蛋白100(GP100)的水泡性口炎病毒(VSV)相結(jié)合,。這種治療方案使得黑色素瘤消退,,并使機(jī)體產(chǎn)生抗腫瘤免疫。
腫瘤反應(yīng)與體內(nèi)T細(xì)胞的持續(xù)存在和激活以及治療相關(guān)性白癜風(fēng)密切相關(guān),。然而,,在接受治療的一部分小鼠中,最初的腫瘤消退往往伴隨著以后的復(fù)發(fā),。為解決這一問(wèn)題,,研究者進(jìn)一步針對(duì)一個(gè)額外的腫瘤抗原,結(jié)合之前的VSV-抗原與ACT相聯(lián)合的策略,,導(dǎo)致100%的受試小鼠持續(xù)發(fā)生治療應(yīng)答,。
總之,該研究結(jié)果表明,,系統(tǒng)性病毒治療結(jié)合表達(dá)抗原的VSV的可以用來(lái)支持和加強(qiáng),,已經(jīng)在臨床上使用的過(guò)繼免疫細(xì)胞治療技術(shù)。(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.