[新聞][轉載]中研院研究重大突破 治療乳癌疫苗 …
http://www.cdnews.com.tw/cdnews_site/docDetail.jsp?docid=100481285
中研院研究重大突破 治療乳癌疫苗有望
http://www.cdnews.com.tw 2008-08-12 22:43:10
王鵬捷/綜合報導
中央研究院針對乳癌幹細胞表面多醣抗原物質的研究，獲得重大突破！基因體研
究中心團隊從乳癌幹細胞表面找到兩個多醣體結構，除了可以研發治療乳癌疫苗，
未來更可以研發出醣晶片，用於早期的癌症檢測上。
中央社12日報導，這項研究成果論文，接連兩篇同時獲刊於國際頂尖的「美國國
家科學院期刊（OnlineEarlyEditionof
PNAS,ProceedingsoftheNationalAcademyof
SciencesoftheUnitedStatesofAmerica）」上。
基因體研究中心副主任陳鈴津解釋，癌症治療的困難點，在於治療之後，癌細胞
仍會復發、也可能轉移，但是如果治療乳癌能從生長源頭的幹細胞下手，可能就能
阻斷癌症生長的源頭；因此，以癌症幹細胞為治療的主要標的，成為最新的研究趨
勢。
在陳鈴津及幹細胞實驗室負責人遊正博特聘研究員的合作下，展開「GloboH」於
癌症幹細胞的研究。由三軍總醫院外科部醫師俞志誠取得來自五十三位乳癌病患的
癌細胞，針對「GloboH」以及「Gb5」在乳癌幹細胞表面的表現作分析。結果，領
先全球，團隊證實「 GloboH」以及「Gb5」都會表現在乳癌幹細胞的表面。
陳鈴津說明，從源頭的乳癌幹細胞上找到兩個多醣體結構「GloboH」和「Gb5」
。研究人員透過小老鼠實驗發現，「GloboH」疫苗針對乳癌細胞及乳癌幹細胞都可
以達到免疫作用，更進一步找到佐劑加強治療，這對醫界未來找尋根治抗乳癌的疫
苗或藥物，將更有希望。
陳鈴津說，目前已上市的有預防型的疫苗，如B型肝炎疫苗和子宮頸癌疫苗；但
是治療型的疫苗世界上還沒有研發出來，她相信遲早會問世。
中研院基因體研究中心助研究員吳宗益指出，從乳癌幹細胞表面上找到「GloboH
」和「Gb5」這兩個多醣體結構，不但可據此研發出治療型的乳癌疫苗，還可以設
計出醣晶片，此醣晶片非常靈敏，只要血液內有極微量的抗體該晶片都能檢測出來
，因而能把乳癌對婦女健康的威脅降到最低。
吳宗益表示，「GloboH」乳癌疫苗已經由院長翁啟惠領導的團隊成功合成，並在
第一期臨床試驗得到良好的免疫反應，將由國內的藥廠引進，繼續作第二期之後的
各項臨床試驗。
http://www.pnas.org/content/early/2008/08/05/0804979105.abstract
Expression of Globo H and SSEA3 in breast cancer stem cells and the
involvement of fucosyl transferases 1 and 2 in Globo H synthesis
1. Wen-Wei Chang*,＋,
2. Chien Hsin Lee*,＋,
3. Peishan Lee*,
4. Juway Lin*,‡,
5. Chun-Wei Hsu*,
6. Jung-Tung Hung*,
7. Jin-Jin Lin*,
8. Jyh-Cherng Yu§,
9. Li-en Shao*,
10. John Yu*,¶,
11. Chi-Huey Wong*,∥, and
12. Alice L. Yu*,∥
+Author Affiliations
1.
*Genomics Research Center and
2.
¶Institute of Cellular and Organismic Biology, Academia Sinica,
Taipei 115, Taiwan;
3.
‡Institute of Biochemical Sciences, National Taiwan University,
Taipei 106, Taiwan; and
4.
§General Surgery, Department of Surgery, Tri-Service General
Hospital, Taipei 114, Taiwan
1.
＋W.-W.C. and C.H.L. contributed equally to this work.
2.
Contributed by Chi-Huey Wong, May 22, 2008 (sent for review April
2, 2008)
Abstract
We examined the expression in breast cancer stem cells (BCSCs) of Globo
H, a potential tumor-associated antigen for immunotherapy of epithelial
cancers including breast cancer. Flow cytometry revealed Globo H
expression in 25/41 breast cancer specimens (61.0%). Non-BCSCs from
25/25 and BCSCs from 8/40 (20%) expressed Globo H. We showed the
expression of stage-specific embryonic antigen 3 (SSEA3), the
pentasaccharide precursor of Globo H, in 31/40 (77.5%) tumors.
Non-BCSCs from 29/31 and BCSCs from 25/40 (62.5%) expressed SSEA3. Like
Globo H, SSEA3 expression in normal tissues was predominately at the
secretory borders of epithelium, where access to the immune system is
restricted. Immunization of mice with Globo H-KLH and α-GalCer induced
antibodies reactive with Globo H and SSEA3, suggesting that a Globo
H-based vaccine will target tumor cells expressing Globo H or SSEA3. We
next sought to reduce Globo H expression by siRNA targeting
fucosyltransferase (FUT) 1 and 2, which mediate alpha-1,2 linkage of
fucose to SSEA3 to generate Globo H. We showed both genes to be
involved in the biosynthesis of Globo H. Moreover, FUT2 expression in
BCSCs was significantly lower than in non-BCSCs harvested from a
primary human breast cancer in NOD/SCID mouse, whereas FUT1 was
slightly lower in BCSCs. Thus, the lower expression of Globo H in BCSCs
may be attributed to less FUT2/FUT1, and to reduced SSEA3 in BCSCs
compared with non-BCSCs. Our findings provide insight into further
development of a Globo H-based vaccine and FUT1/FUT2-targeted therapy
for breast cancer.
http://www.pnas.org/content/early/2008/08/07/0804923105.abstract
Glycan microarray of Globo H and related structures for quantitative
analysis of breast cancer
1. Cheng-Chi Wang*,＋,
2. Yen-Lin Huang*,＋,
3. Chien-Tai Ren*,
4. Chin-Wei Lin*,
5. Jung-Tung Hung*,
6. Jyh-Cherng Yu‡,
7. Alice L. Yu*,§,
8. Chung-Yi Wu*,§, and
9. Chi-Huey Wong*,§
-Author Affiliations
1.
*The Genomics Research Center, Academia Sinica, Taipei, Taiwan;
2.
＋Institute of Biochemical Science, National Taiwan University,
Taipei, Taiwan; and
3.
‡Tri-Service General Hospital, Taipei, Taiwan
1.
Contributed by Chi-Huey Wong, May 23, 2008 (sent for review
January 1, 2008)
Abstract
Cancer-associated carbohydrate antigens are often found on the surface
of cancer cells. Understanding their roles in cancer progression will
lead to the development of new therapeutics and high-sensitivity
diagnostics for cancers. Globo H is a member of this family, which is
highly expressed on breast cancer cells. Here, we report the
development of a glycan microarray of Globo H and its analogs for
measurement of the dissociation constants on surface (K D,surf) with
three different monoclonal antibodies (VK-9, Mbr1, and anti-SSEA-3), to
deduce their binding specificity. The glycan microarray was also used
to detect the amount of antibodies present in the plasma of breast
cancer patients and normal blood donors. It was shown that the amount
of antibodies against Globo H from breast cancer patients were
significantly higher than normal blood donors, providing a new tool for
possible breast cancer diagnosis. Compared with the traditional ELISA
method, this array method required only atto-mole amounts of materials
and is more effective and more sensitive (5 orders of magnitude). The
glycan microarray thus provides a new platform for use to monitor the
immune response to carbohydrate epitopes after vaccine therapy or
during the course of cancer progression.
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