(3.238.96.184) 您好!臺灣時間:2021/05/15 05:47
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果

詳目顯示:::

我願授權國圖
: 
twitterline
研究生:魏孝倫
研究生(外文):Show Len Wei
論文名稱:利用酵素-抗體連結物活化前驅藥物治療癌症之轉移
論文名稱(外文):Targeted enzyme activation of anti-neoplastic prodrugs for therapy of metastasis
指導教授:劉寶瑋,羅傅倫
指導教授(外文):Pao Wei Liu, Steven R. Roffler
學位類別:碩士
校院名稱:輔仁大學
系所名稱:生物學研究所
學門:生命科學學門
學類:生物學類
論文種類:學術論文
論文出版年:1995
畢業學年度:83
語文別:中文
論文頁數:68
中文關鍵詞:前驅藥物單株抗體癌症轉移旁觀者效應
外文關鍵詞:prodrugmonoclonal antibodytumor metastasisbystander effect
相關次數:
  • 被引用被引用:0
  • 點閱點閱:501
  • 評分評分:
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:0
本實驗室發展的是屬於標的治療法之一的「抗原-抗體連結物活化前驅抗
癌藥物治療癌症」( antibody -directed enzyme prodrug therapy,
ADEPT),先前利用ADEPT治Balb/c 老鼠的腹腔腫瘤已得到良好效果,為了進
一步探討ADEPT的效能,本論文將研究其是否具有旁觀者效應(bystander
effect),以及ADEPT對於微小轉移(micrometa- stasis)的治療效果。
ADEPT是利用對抗癌細胞相關抗原的單株抗體連結到酵素而形成連結物(
conjugate),治療方式是先給予conjugate, 再投予親水性的前驅抗癌藥
物(prodrug),prodrug會被連結物上的酵素活化而轉變成水性的抗癌藥物(
drug),此藥易通過細胞膜而毒殺細胞,在ADEPT模式中,除了能毒殺表現抗
原的癌細胞(antigen-positive cancer cell),若也能殺不表現抗原的癌
細胞( antigen-negative cancer cell ),則稱之為旁觀者效應(
bystander effect)。本論文筆者利用RH1抗體可以專一性認識AS-30D 老
鼠肝癌細胞而不能認識N1S1老鼠肝癌細胞的特性,將AS-30D細胞和N1S1細
胞作1:1的混合,再以ADEPT模式給藥,結果顯示,有99% 與AS-30D細胞混合
的N1S1細胞被殺死,發現在我們的 ADEPT系統中有明顯的Bystander
effect 存在。以往常用化學治療法或全身性放射治療法治療轉移,但是會
同時傷害正常組織,且也無法百分之百的治癒轉移的癌細胞。因此,我們嘗
試用ADEPT 的方法來治療癌細胞。本文筆者發展對轉移性B16黑色素癌細
胞(B16 melanoma cell)之單株抗體用於ADEPT的治療法。我們選 B16/
F10 model作為動物模示。我們做出一系列對抗B16/F10單株抗體及對抗
B16/F10/L cells 的抗體(anti-B16/F10/L mAbs),同時測定這些單株抗體
對B16/F10,B16/F10/L cells,淋巴細胞,紅血球細胞之結合力。由兩次做
融合瘤單株抗體的結果,我們推論(a)B16/F10 cells可能具有很多
subpopulations,轉移性較高的subpopulation較不易引起免疫反應,因此
我們做出的抗體不會認識轉移到肺上的細胞,(b)B16 /F10/L cells具有較
高轉移性但不易引起免疫反應,推測其抗原可能為醣類。

We have attempted to increase drug specificity by using ADEPT
(antibody-directed enzyme prodrug therapy). ADEPT involves a
two-step process for cancer therapy. An enzyme which can
convert a prodrug to an anti-neoplastic drug is linked to a mAb
that binds to tumor-associated antigens. A prodrug is then
administrated which can be converted to active drug by enzyme
at the tumor site. The activated drug diffuses into the tumor
cells and kill the cancer cells. Chemotherapy and whole-body
radiation used for metsatasis therapy generally cause large
damage to normal tissue before every cancer cell can be killed.
An alternative strategy is cells form tumor colonies in the
lungs of C57BL/6 mice after to use ADEPT to treat metastatic
lesions. A panel of mAbs was produced against B16(B16/F10,B16/
F10/L)melanoma cells which metastasis, and this problem was
discussed in this work. The have metastatic potential. We found
that anti-B16/F10 mAbs lose their antigens after metastasis.
Subclass of all the mAbs against B16/F10/L cells were IgM. We
suggest that B16 melanoma cells with low metastatic potential
are immunodominant, and we propose that antigens recognized by
anti-B16/F10/L mAbs are A major advantage of ADEPT is the
potential to generate a "bystander effect" in which tumor cells
that are inaccessible to antibody conjugates are still killed
by drug generated by enzyme localized at nearby antigen-
positive cells. The"bystander effect" was therefore
investigeted in our system. MAb RH1 which binds to AS-30D rat
hepatoma cells but does not bind to N1S1 rat hepatoma cells was
used to study the in vitro bystander effect. We found that 99%
of N1S1 cells mixed with equal numbers of AS-30D cells were
killed when treated by the ADEPT method. Only 1 in 50 cells
were required to express antigen to generate a potent bystander
effect. The data shows a significant bystander effect exist in
our ADEPT system.

QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top