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血管新生抑制分子・転移抑制分子を用いた固形癌の遺伝子治療法の開発

使用血管生成抑制分子和转移抑制分子开发实体瘤基因治疗方法

基本信息

批准号：
12217107
负责人：
上野光
金额：
$ 2.88万
依托单位：
University of Occupational and Environmental Health, Japan
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research on Priority Areas (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至无数据
项目状态：
已结题

项目摘要

腫瘍は血管新生を誘導し栄養路を確保しながら成長する。この腫瘍血管新生を抑制できれば効率的な癌の退縮が達成される可能性が高い。強力な血管新生因子であるVEGF(Vascular endothelial growth factor)に注目し、その作用を特異的に抑制して抗腫瘍血管新生療法の有用性を検討した。ヒト肺癌由来の14種の細胞を準備して培養上清中のVEGFを測定すると、すべての癌細胞でVEGFが検出され、その産生能と造腫瘍能には相関を認めた。細胞外領域のみの可溶型VEGF受容体(flt-1)を作成しアデノウイルスに組み込んだ。産生される可溶型受容体はVEGFに結合しその作用を特異的に抑制した。ヌードマウス皮下に癌細胞を移植し生着したあと、可溶型VEGF受容体遺伝子を筋肉内に1度だけ導入すると、可溶型受容体が循環血中に検出され、腫瘍の成育はある程度の大きさで止まり以後はむしろ退縮した。腫瘍内では血管新生が阻害され癌細胞のアポトーシスが亢進していた。可溶型VEGF受容体は造腫瘍能を検討した6種の癌細胞のうち5種で有効であり、汎用性も期待できる。可溶型分子であるため癌細胞すべてに遺伝子導入される必要がなく、さらに標的部位より遠隔地での発現でも効果が期待できる。また細胞増殖には直接影響を与えないので副作用も少ないと期待される。組換え蛋白としての投与も現実的であり、癌の新たな治療戦略として有望である。

Tumors can induce angiogenesis, maintain their path, and ensure their growth. There is a high possibility that tumor angiogenesis can be suppressed and cancer regression can be achieved efficiently. The powerful angiogenic factor VEGF (Vascular endothelial growth factor) is attracting attention, and its specific action is inhibiting, and its usefulness in anti-tumor angiogenesis therapy is also known. From the origin of lung cancer, 14 types of cells were prepared, VEGF was measured in the culture supernatant, VEGF was measured in cancer cells, and the ability to produce tumors and the ability to produce tumors were recognized. Soluble VEGF receptor (flt-1) in the extracellular domain is produced by しアデノウイルスに组み込んだ. It produces a soluble receptor that binds to VEGF and has a specific inhibitory effect. The transplantation of cancer cells under the skin was carried out and the soluble VEGF receptor was introduced into the muscle at the first degree. The soluble receptor does not appear in the circulating blood, and the degree of growth of the tumor does not increase, and the degree of growth does not stop, and the disease shrinks later. In the tumor, angiogenesis is hindered and cancer cells are inhibited and cancer cells are increased. Soluble VEGF receptors are effective in creating tumors and can treat 6 types of cancer cells and 5 types of cancer cells, and their general applicability is expected. Soluble molecules are required to be introduced into cancer cells, and the desired effect is expected from a distance at the target site. It has a direct effect on cell proliferation and side effects and is expected to be less. The combination of new proteins, new investment strategies, and new strategies for cancer treatment are promising.