一種鼻咽癌細胞的標記胜肽

專利類型

發明

專利國別 (專利申請國家)

中華民國

專利申請案號

092117944

專利證號

I262192

專利獲證名稱

一種鼻咽癌細胞的標記胜肽

專利所屬機關 (申請機關)

國立臺灣大學

獲證日期

2006/09/21

技術說明

利用噬菌體展示胜肽庫(phage-displayed random peptide library)與鼻咽癌細胞(NPC cells)作用我們找出一特殊胜肽,將之用來做標的化療,作為治療鼻咽癌的另一療法.此一新穎的12 個胺基酸胜肽,可用來做導送藥物到NPC 腫瘤組織.在長有NPC 異體腫瘤(xenograft)之免疫失全小鼠(SCID mice)中,此胜肽也能特殊的與腫瘤細胞結合,但不會與正常細胞結合. 同樣的若對SCID mice 帶有NPC xenograft 而打入胜肽---微脂體(帶平常藥量的五分之一的化療藥物doxorubicin)時,則可見小鼠之xenograft 變成很小.與對照組比起來約為其12%大小, 而此變小之腫瘤在顯微鏡下竟是大部份為壞死及凋亡的死細胞及很小部份活的癌細胞; 同時小鼠體重及所有器官都很正常.這個研究結果非常令人鼓舞,因為用所發現之新穎胜肽所帶裝有1/5 量之化療藥物之微脂體既可抑制腫瘤生長,又沒有副作用,這對晚期NPC 病人而言是一大福音. 因此, 我們也以此胜肽向台灣及美國申請到專利, 其號碼為: Taiwan Patent#I262192(2006/9/21~2023/6/30); U.S. Patent#7,238,665B2(2007/7/3~2024/5/9). We have identified a 12-mer peptide (L-peptide) specifically binding to Nasopharyngeal carcinoma (NPC) cells with a phage displayed random peptide library. The L-phage and synthetic L-peptide bound to the tumor cell surfaces of most NPC cell lines and biopsy specimens, but not normal nasal mucosal cells, and the L-peptide–linked liposomes containing fluorescent substance (L-peptide-Lipo-HPTS) were capable of binding to and translocating across plasma membranes. L-Peptide–linked liposomes that carried doxorubicin (L-peptide-Lipo-Dox) caused marked cytotoxicity in NPC cells. In SCID mice bearing NPC xenografts, the L-phages specifically bound to the tumor mass, an effect that was inhibited by competition with synthetic L-peptide. In addition, the L-peptide-Lipo-Dox suppressed tumor growth better than Lipo-Dox. These results indicate that the novel L-peptide specifically binds NPC cells and is a good candidate for targeted drug delivery to NPC solid tumors.

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