肝癌細胞特異性胜肽及其應用
  ‧ 專利名稱 肝癌細胞特異性胜肽及其應用
  ‧ 專利證書號 I372866
  ‧ 專利權人 中研院
  ‧ 專利國家
    (申請日)
美國 (2008/11/18)
中華民國 (2008/11/19)
中國 (2010/07/14)
  ‧ 發明人 吳漢忠, 林欽塘, 羅元駿,
 
技術摘要:
肝細胞癌(HCC)是全世界癌症死亡之第四大肇因。日益蓬勃的分子癌病學知識發展出新穎的治療策略,現正持續研發,以治療此種疾病。於此,我們使用噬菌體顯現法鑑別新穎的胜肽,包括SP94,其可專一結合至HCC細胞。在活體外,噬菌體純系PC94可結合至HCC細胞系。在活體內,於帶有人類HCC異體移植物之SCID小鼠中,PC94可專一歸向腫瘤組織,但不會歸向正常臟器。該歸向能力可被合成胜肽SP94所競爭抑制。PC94定位於腫瘤組織中,但在經SP94競爭之腫瘤組織或正常器官中,則未偵測到其存在。此外,在取自HCC病患之手術樣本中,PC94可辨識腫瘤組織但不會辨識非腫瘤組織,其陽性率為61.3%(19/31)。SP94與微脂體阿黴素(doxorubicin)之共軛結合可產生一種靶向藥物傳遞系統,其可透過增強的腫瘤凋亡作用及降低的腫瘤血管生成作用,而增強對抗HCC異體移植物之治療功效。我們的結果證實SP94可改良對於罹患後期HCC病患之全身性治療。

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer death worldwide. Novel treatment strategies derived from increased knowledge of molecular oncology are constantly being developed to cure this disease. Here, we used phage display to identify novel peptides, including (SP94), which binds specifically to HCC cells. In vitro, the phage clone PC94 binds to HCC cell lines. In vivo, PC94 homed specifically to tumor tissues but not to normal visceral organs in SCID mice bearing human HCC xenografts. The homing ability could be competitively inhibited by synthetic peptide, SP94. PC94 localized to tumor tissues but could not be detected in SP94-competed tumor tissues or in normal organs. In addition, PC94 recognized the tumor tissue but not non-tumor tissue in surgical specimens from HCC patients, with a positive rate of 61.3% (19/31). With the conjugation of SP94 and liposomal doxorubicin, a targeted drug delivery system enhanced the therapeutic efficacy against HCC xenografts through enhanced tumor apoptosis and decreased tumor angiogenesis. Our results indicate that SP94 can improve the systemic treatment of patients with advanced HCC.



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