Dendritic cell based PSMA immunotherapy for prostate cancer using a CD40-targeted adenovirus vector.
Dendritic cell based PSMA immunotherapy for prostate cancer using a CD40-targeted adenovirus vector.
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DOI：
10.1371/journal.pone.0046981
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Mathis JM
中科院分区：
文献类型：
--
作者：
Williams BJ;Bhatia S;Adams LK;Boling S;Carroll JL;Li XL;Rogers DL;Korokhov N;Kovesdi I;Pereboev AV;Curiel DT;Mathis JM
人类前列腺肿瘤疫苗和基因治疗试验使用离体方法用前列腺特异性膜抗原（PSMA）初始树突状细胞（dc）已经取得了一定程度的成功，但迄今为止，树突状细胞的长期离体操作限制了该方法的广泛临床应用。我们的目标是通过cd40靶向腺病毒载体将PSMA直接传递到dc，作为激活和抗原呈递到t细胞的有效手段，从而改善肿瘤抗原的癌症疫苗接种。为了验证这种方法，我们通过生成表达人类PSMA的小鼠RM-1前列腺癌细胞系的克隆衍生物（RM-1-PSMA细胞）建立了小鼠前列腺癌模型。为了最大化抗原在靶细胞中的呈递，用表达干扰素- γ (ad5 - ifn - γ)的Ad载体转导RM-1细胞，诱导MHC I类和TAP蛋白表达。给体外感染了cd40靶向Ad5-huPSMA的DCs，以及直接腹腔注射载体，导致针对ad5 - ifn作为靶细胞预处理的RM-1-PSMA细胞的高水平肿瘤特异性CTL反应。在RM-1-PSMA模型中，CD40靶向与Ad5-IFNγ联合可显著提高编码PSMA的Ad5-huPSMA的抗肿瘤疗效。这些结果表明，cd靶向腺病毒递送PSMA可能在临床上有效地用于前列腺癌免疫治疗。
Human prostate tumor vaccine and gene therapy trials using ex vivo methods to prime dendritic cells (DCs) with prostate specific membrane antigen (PSMA) have been somewhat successful, but to date the lengthy ex vivo manipulation of DCs has limited the widespread clinical utility of this approach. Our goal was to improve upon cancer vaccination with tumor antigens by delivering PSMA via a CD40-targeted adenovirus vector directly to DCs as an efficient means for activation and antigen presentation to T-cells. To test this approach, we developed a mouse model of prostate cancer by generating clonal derivatives of the mouse RM-1 prostate cancer cell line expressing human PSMA (RM-1-PSMA cells). To maximize antigen presentation in target cells, both MHC class I and TAP protein expression was induced in RM-1 cells by transduction with an Ad vector expressing interferon-gamma (Ad5-IFNγ). Administering DCs infected ex vivo with CD40-targeted Ad5-huPSMA, as well as direct intraperitoneal injection of the vector, resulted in high levels of tumor-specific CTL responses against RM-1-PSMA cells pretreated with Ad5-IFNγ as target cells. CD40 targeting significantly improved the therapeutic antitumor efficacy of Ad5-huPSMA encoding PSMA when combined with Ad5-IFNγ in the RM-1-PSMA model. These results suggest that a CD-targeted adenovirus delivering PSMA may be effective clinically for prostate cancer immunotherapy.
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影响因子：
4.6
作者：
Fishman, Mayer
通讯作者：
Fishman, Mayer
影响因子：
12.4
作者：
Pereboev, AV;Nagle, JM;Blackwell, JL
通讯作者：
Blackwell, JL
DOI：
10.1016/0960-0760(95)00001-g
发表时间：
1995-05-01
影响因子：
4.1
作者：
BALEY, PA;YOSHIDA, K;THOMPSON, TC
通讯作者：
THOMPSON, TC
影响因子：
5.5
作者：
Brandao, JG;Scheper, RJ;de Gruijl, TD
通讯作者：
de Gruijl, TD
影响因子：
2.8
作者：
Fuessel, Susanne;Meye, Axel;Wirth, Manfred P.
通讯作者：
Wirth, Manfred P.