瑞典卡羅林斯卡醫(yī)學(xué)院日前發(fā)表公告說(shuō),，該機(jī)構(gòu)研究人員研制出一種可抑制惡性腫瘤生長(zhǎng)的新型DNA（脫氧核糖核酸）疫苗，實(shí)驗(yàn)顯示這種疫苗無(wú)副作用,。
當(dāng)惡性腫瘤超過(guò)幾個(gè)毫米時(shí),，需要形成新的血管為腫瘤提供營(yíng)養(yǎng)和氧氣。因此,，阻止血管的生長(zhǎng)是治療惡性腫瘤的思路之一,。蛋白質(zhì)DLL4是形成血管的必要成分，如果能抑制腫瘤細(xì)胞中的DLL4蛋白質(zhì),，將使新血管失去功能,，從而大大減緩腫瘤的生長(zhǎng)速度。
研究人員據(jù)此研制出了這種DNA疫苗,。經(jīng)對(duì)患有乳腺癌的小白鼠進(jìn)行試驗(yàn)，證明接種疫苗的小白鼠體內(nèi)產(chǎn)生了可抑制DLL4蛋白質(zhì)的抗體,，阻止了體內(nèi)乳腺腫瘤的生長(zhǎng),，而且沒(méi)有引起任何不良反應(yīng)，也未影響小白鼠的傷口愈合,。
研究人員皮耶特拉斯稱,，選擇乳腺癌作為試驗(yàn)?zāi)繕?biāo)是因?yàn)槿橄倌[瘤帶有大量的DLL4蛋白質(zhì)。研究人員希望能將這種疫苗用于乳腺癌的術(shù)后治療,，防止腫瘤復(fù)發(fā),。(生物谷Bioon.com)
更多閱讀
Nature：刺激新抗原或可創(chuàng)造有效癌癥疫苗
PNAS：開(kāi)發(fā)出以植物為主的癌癥疫苗
癌癥疫苗專題
治療性癌癥疫苗開(kāi)創(chuàng)癌癥治療新領(lǐng)域
STEM CELLS：人類(lèi)干細(xì)胞可用于制造結(jié)腸癌疫苗
生物谷推薦原文出處：
Oncogene doi: 10.1038/onc.2010.176
Therapeutic efficacy of a DNA vaccine targeting the endothelial tip cell antigen delta-like ligand 4 in mammary carcinoma
B K Haller1,2,6, A Br?ve1,2, E Wallgard3,7, P Roswall3, V G Sunkari4, U Mattson5, D Halleng?rd1,2, S-B Catrina4, M Hellstr?m5,7 and K Pietras3
1Department of Virology, Swedish Institute for Infectious Disease Control, Stockholm, Sweden
2Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden
3Division of Vascular Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden
4Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
5Bioinvent International, Lund, Sweden
6Current address: Department of Oncology and Pathology, Cancer Center Karolinska, Karolinska Institutet, Stockholm, Sweden.
7Current address: Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden.
The Notch ligand delta-like ligand 4 (DLL4) is an essential component expressed by endothelial tip cells during angiogenic sprouting. We have described a conceptually novel therapeutic strategy for targeting tumor angiogenesis and endothelial tip cells based on DNA vaccination against DLL4. Immunization with DLL4-encoding plasmid DNA by in vivo electroporation severely retarded the growth of orthotopically implanted mammary carcinomas in mice by induction of a nonproductive angiogenic response. Mechanistically, vaccination brought about a break in tolerance against the self-antigen, DLL4, as evidenced by the production of inhibitory and inherently therapeutic antibodies against mouse DLL4. Importantly, no evidence for a delayed wound healing response, or for toxicity associated with pharmacological blockade of DLL4 signaling, was noted in mice immunized with the DLL4 vaccine. We have thus developed a well-tolerated DNA vaccination strategy targeting the endothelial tip cells and the antigen DLL4 with proven therapeutic efficacy in mouse models of mammary carcinoma; a disease that has been reported to dramatically induce the expression of DLL4. Conceivably, induction of immunity toward principal mediators of pathological angiogenesis could provide protection against recurrent malignant disease in the adjuvant setting.
