Oncogene：新型DNA抗癌疫苗问世

       当恶性肿瘤超过几个毫米时，需要形成新的血管为肿瘤提供营养和氧气。因此，阻止血管的生长是治疗恶性肿瘤的思路之一。蛋白质DLL4是形成血管的必要成分，如果能抑制肿瘤细胞中的DLL4蛋白质，将使新血管失去功能，从而大大减缓肿瘤的生长速度。

       研究人员据此研制出了这种DNA疫苗。经对患有乳腺癌的小白鼠进行试验，证明接种疫苗的小白鼠体内产生了可抑制DLL4蛋白质的抗体，阻止了体内乳腺肿瘤的生长，而且没有引起任何不良反应，也未影响小白鼠的伤口愈合。

       研究人员皮耶特拉斯称，选择乳腺癌作为试验目标是因为乳腺肿瘤带有大量的DLL4蛋白质。研究人员希望能将这种疫苗用于乳腺癌的术后治疗，防止肿瘤复发。(生物谷Bioon.com)

       生物谷推荐原文出处：

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.