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ovarian cancer-specific vaccine therapy by carrier cell

载体细胞的卵巢癌特异性疫苗治疗

基本信息

批准号：
20591952
负责人：
HAMADA Katsuyuki
金额：
$ 2.91万
依托单位：
Ehime University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2008
资助国家：
日本
起止时间：
2008 至 2010
项目状态：
已结题

项目摘要

GFP-introduced non small cell lung cancer A549 cells infected with oncolytic adenovirus, AdE3-IAI.3B was injected into the mouse subcutaneous tumors and DNA contents of GFP and AdE3-IAI.3B in the tumors peaked one day later and disappeared two weeks later. EHK-2 cell was established from A549 cells by limiting dilution and showed the 10 time higher antitumor effect than the original A549 cells. OVHM subcutaneous tumor formation was rejected in 40% of mice after the subcutaneous injection of AdE3-IAI.3B-infected EHK-2 carrier cells. This indicated that xenogenic antitumor immunity was introduced after the injection of carrier cells. The infection condition of carrier cells at 200MOI (multiplicity of infection) and 33 hours showed the best antitumor effect. The morphology of non-infected carrier cells was not changed but AdE3-IAI.3B-infected carrier cells showed the nuclear membrane lobulation. After the freeze and thaw of carrier cells, the lobulated nuclear membrane was ruptured and the adenovirus particles were released from the nucleus into the cytoplasm. Under these infection conditions, the in vitro antitumor effect increased by 20% and 90% of mouse showed the complete tumor reduction after the prior immunization of adenovirus. In the mouse model of intraperitoneal dissemination of OVHM ovarian cancer cells, the intraperitoneal injection of AdE3-IAI.3B-infected carrier cells did not cure any mice but the carrier cells infected with Ad-mGM-CSF and AdE3-IAI.3B showed the complete tumor reduction in all treated mice after the prior adenoviral immunization. The tumor formation of OVHM ovarian cancer cells was rejected in all complete tumor reduced mice treated with carrier cells and self-antitumor immunity was introduced in these mice.

将感染溶瘤腺病毒AdE3-IAI.3B的引入GFP的非小细胞肺癌A549细胞注射到小鼠皮下肿瘤中，肿瘤中GFP和AdE3-IAI.3B的DNA含量一天后达到峰值，两周后消失。 EHK-2细胞是由A549细胞通过有限稀释建立的，其抗肿瘤效果比原始A549细胞高10倍。皮下注射AdE3-IAI.3B感染的EHK-2载体细胞后，40%的小鼠拒绝了OVHM皮下肿瘤的形成。这表明注射载体细胞后引入了异种抗肿瘤免疫。载体细胞在200MOI（感染复数）和33小时的感染情况下显示出最好的抗肿瘤效果。未感染的载体细胞的形态没有改变，但AdE3-IAI.3B感染的载体细胞显示核膜分叶。载体细胞冻融后，分叶状核膜破裂，腺病毒颗粒从细胞核释放到细胞质中。在这些感染条件下，体外抗肿瘤效果增加了20%，并且90%的小鼠在腺病毒预先免疫后显示肿瘤完全缩小。在OVHM卵巢癌细胞腹膜内传播的小鼠模型中，腹膜内注射AdE3-IAI.3B感染的载体细胞没有治愈任何小鼠，但感染Ad-mGM-CSF和AdE3-IAI.3B的载体细胞在先前的腺病毒免疫后显示所有治疗小鼠的肿瘤完全缩小。在用载体细胞治疗的所有肿瘤完全减少的小鼠中，OVHM卵巢癌细胞的肿瘤形成被拒绝，并且在这些小鼠中引入了自身抗肿瘤免疫。