PTEN knockout prostate cancer as a model for experimental immunotherapy.
PTEN knockout prostate cancer as a model for experimental immunotherapy.
复制标题
PTEN 敲除前列腺癌作为实验性免疫治疗的模型。
DOI：
10.1016/j.juro.2008.08.124
复制
发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Kasahara,Noriyuki
中科院分区：
文献类型：
--
作者：
Haga,Kazunori;Tomioka,Atsushi;Liao,Chun-Peng;Kimura,Takahiro;Matsumoto,Hiroshi;Ohno,Izumi;Hermann,Kip;Logg,ChristopherR;Jiao,Jing;Tanaka,Motoyoshi;Hirao,Yoshihiko;Wu,Hong;Kruse,CarolA;Roy-Burman,Pradip;Kasahara,Noriyuki
由于缺乏相关的免疫活性动物肿瘤模型，检测前列腺癌的免疫抑制策略一直受到阻碍。现在，前列腺特异性PTEN敲除小鼠的最新发展提供了这种机会，该小鼠显示出由前列腺上皮产生的真正腺癌的自发发展，并且比任何先前的模型更忠实地再现了人类疾病。我们研究了使用来自这个模型的肿瘤细胞来测试肿瘤疫苗接种和过继免疫策略的可行性prostate cancer.Materials和MethodsPTEN-CaP 8腺癌细胞来自双等位基因PTEN基因敲除前列腺癌模型被用来接种nontumor轴承同窝出生的队友。通过混合淋巴细胞-肿瘤反应从接种疫苗的小鼠的脾细胞产生肿瘤特异性效应细胞，并在体外检查抗增殖作用和细胞因子产生。荧光素酶标记的PTEN-CaP 8皮下肿瘤的疫苗接种或过继免疫治疗的效果进行了监测，通过肿瘤体积测量和非侵入性bioluminescence imaging.ResultsVaccination的同窝小鼠与辐照的PTEN-CaP 8细胞显示出显着的预防效果对随后的肿瘤的挑战。从接种的同窝小鼠收获的效应细胞在与PTEN-CaP 8靶细胞共孵育后显示出显著的干扰素-γ分泌，并且它们能够在体外有效地抑制靶细胞生长。瘤内过继转移效应细胞导致显着的生长抑制预先建立的前列腺肿瘤在vivo.ConclusionsThe PTEN敲除模型作为一个非常有用的模型，在其中调查肿瘤细胞疫苗接种和过继免疫策略的背景下，真正的前列腺腺癌。这种模型应该加速开发有效的人类前列腺癌免疫疗法的努力。
PurposeTesting immunotherapeutic strategies for prostate cancer has been impeded by the lack of relevant tumor models in immunocompetent animals. This opportunity is now provided by the recent development of prostate specific PTEN knockout mice, which show spontaneous development of true adenocarcinoma arising from prostate epithelium and more faithfully recapitulate the human disease than any previous model. We investigated the feasibility of using tumor cells derived from this model to test tumor vaccination and adoptive immunotherapeutic strategies for prostate cancer.Materials and MethodsPTEN-CaP8 adenocarcinoma cells derived from the biallelic PTEN knockout prostate cancer model were used to vaccinate nontumor bearing litter mates. Tumor specific effector cells were generated from splenocytes of vaccinated mice by mixed lymphocyte-tumor reactions, and antiproliferative effects and cytokine generation were examined in vitro. The effect of vaccination or adoptive immunotherapy on luciferase marked PTEN-CaP8 subcutaneous tumors was monitored by tumor volumetric measurements and noninvasive bioluminescence imaging.ResultsVaccination of litter mate mice with irradiated PTEN-CaP8 cells showed a significant prophylactic effect against the subsequent tumor challenge. Effector cells harvested from vaccinated litter mates showed significant interferon-γ secretion upon co-incubation with PTEN-CaP8 target cells and they were capable of efficient target cell growth inhibition in vitro. Intratumor adoptive transfer of effector cells resulted in significant growth inhibition of preestablished prostate tumors in vivo.ConclusionsThe PTEN knockout model serves as a highly useful model in which to investigate tumor cell vaccination and adoptive immunotherapeutic strategies in the context of true adenocarcinoma of the prostate. This model should accelerate efforts to develop effective immunotherapies for human prostate cancer.
登录
查看更多内容
影响因子：
50.3
作者：
Wang, SY;Gao, J;Wu, H
通讯作者：
Wu, H
反对 R-3327 Dunning H 肿瘤前列腺起源的争论
DOI：
10.1007/bf02899660
发表时间：
1992
期刊：
Virchows Archiv B
影响因子：
--
作者：
Heinz;U. Rausch;M. Steinhoff;J. Seitz;M. Bacher;M. Papotti;G. Bussolati;P. Tuohimaa;G. Aumüller
通讯作者：
G. Aumüller
影响因子：
45.3
作者：
Dudley, ME;Wunderlich, JR;Rosenberg, SA
通讯作者：
Rosenberg, SA
DOI：
10.1002/1097-0045(20000601)43:4
发表时间：
2000-06
期刊：
The Prostate
影响因子：
--
作者：
Thelma R. Tennant;Hyung Kim;M. Sokoloff;C. Rinker-Schaeffer
通讯作者：
Thelma R. Tennant;Hyung Kim;M. Sokoloff;C. Rinker-Schaeffer
影响因子：
11.2
作者：
Gade, TPF;Hassen, W;Sadelain, M
通讯作者：
Sadelain, M