T cells sensitized with breast tumor progenitor cell vaccine have therapeutic activity against spontaneous HER2/neu tumors.
T cells sensitized with breast tumor progenitor cell vaccine have therapeutic activity against spontaneous HER2/neu tumors.
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DOI：
10.1007/s10549-011-1912-5
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发表时间：
2012-07
影响因子：
3.8
通讯作者：
Plautz, Gregory E.
中科院分区：
文献类型：
--
作者：
Wang, Li-Xin;Plautz, Gregory E.
肿瘤祖细胞对于肿瘤的发生和复发至关重要，因此它们是重要的治疗靶点。我们测试了T细胞是否可以识别乳腺癌祖细胞表达的肿瘤抗原，并获得针对已建立的转移或延迟自发性肿瘤发作的治疗活性。乳腺肿瘤来源于HER 2/neu转基因小鼠，并在选择祖细胞的条件下体外增殖，然后将其用作辐照的全细胞疫苗。从疫苗引流淋巴结中分离最近致敏的T细胞的一个小亚群，然后在体外活化以实现数量扩增。我们表明，肿瘤祖细胞疫苗逆转了对已知HER 2/neu表位的耐受性，否则会被Treg细胞抑制。由于Neuneg亚克隆也诱导了针对乳腺肿瘤的Th 1型免疫应答，因此识别了其他共有的肿瘤抗原。体外活化淋巴结T细胞的连续转移介导了来自多个独立来源的乳腺肿瘤细胞系的已建立转移的消退。此外，过继转移效应T细胞到Neu-tolerant小鼠，几个月前自发性肿瘤的发病，显着推迟肿瘤的发展。有趣的是，T细胞介导的转移瘤溶解刺激了对HER 2/neu以及其他共有抗原的IgG应答。总之，肿瘤祖细胞含有可导致交叉保护性T细胞应答的共享抗原。此外，在免疫介导的肿瘤破坏过程中获得的抗原以有利于耐受逆转和IG类转换的方式呈递。这些互补的效应机制可能通过消除难治性乳腺癌干细胞来增强治疗。
Cancer progenitor cells are critical for tumor initiation and recurrence so they are an important therapeutic target. We tested whether T cells could recognize tumor antigens expressed by breast cancer progenitor cells and acquire therapeutic activity against established metastases or delay onset of spontaneous tumors. Breast tumors were derived from HER2/neu transgenic mice and propagated in vitro under conditions that selected progenitor cells which were then used as an irradiated whole cell vaccine. A minor subset of recently-sensitized T cells was isolated from vaccine-draining lymph nodes then activated in vitro to achieve numerical expansion. We show that the tumor progenitor cell vaccines reversed tolerance to a known HER2/neu epitope, otherwise inhibited by Treg cells. Additional shared tumor antigens were recognized because a Neuneg subclone also induced a Th1 type immune response against breast tumors. Adoptive transfer of in vitro activated lymph node T cells mediated regression of established metastases from multiple independently derived breast tumor lines. Moreover, adoptive transfer of effector T cells into Neu-tolerant mice, months before the onset of spontaneous tumors, significantly postponed tumor development. Interestingly, T-cell mediated lysis of metastases stimulated an IgG response to HER2/neu as well as other shared antigens. In summary, tumor progenitor cells contain shared antigens which can lead to a cross-protective T cell response. Moreover, antigens acquired during immune-mediated tumor destruction are presented in a manner conducive to reversal of tolerance and Ig class switching. These complementary effector mechanisms might augment therapy by eliminating refractory breast cancer stem cells.
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影响因子：
3.6
作者：
Freudenberg, Jaclyn A.;Wang, Qiang;Katsumata, Makoto;Drebin, Jeffrey;Nagatomo, Izumi;Greene, Mark I.
通讯作者：
Greene, Mark I.
影响因子：
11.2
作者：
Brown CE;Starr R;Martinez C;Aguilar B;D'Apuzzo M;Todorov I;Shih CC;Badie B;Hudecek M;Riddell SR;Jensen MC
通讯作者：
Jensen MC
募集高危险性CD8（+）T细胞的潜在池募集到抗肿瘤免疫反应中。
DOI：
10.1084/jem.20042167
发表时间：
2005-05-16
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Ercolini AM;Ladle BH;Manning EA;Pfannenstiel LW;Armstrong TD;Machiels JP;Bieler JG;Emens LA;Reilly RT;Jaffee EM
通讯作者：
Jaffee EM
影响因子：
11.5
作者：
O'Brien, Catherine Adell;Kreso, Antonija;Jamieson, Catriona H. M.
通讯作者：
Jamieson, Catriona H. M.
影响因子：
3.5
作者：
RAVDIN, PM;CHAMNESS, GC
通讯作者：
CHAMNESS, GC