以免疫治療(Immunotherapy)手段醫治癌症,絕對是人類在醫學界踏出的「月球一小步」;1672Please respect copyright.PENANAOUnwDDf8L4
2018年的醫學諾貝爾得獎者,亦是因為對免疫治療方面作出了無比重要的貢獻因而獲獎。1672Please respect copyright.PENANA64NzHp4S6O
1672Please respect copyright.PENANAyOV5CZwAvw
對比傳統的化療,免疫治療不但不會引起脫髮等副作用,病人的存活率更會比傳統化療的顯著為長,但略為遺憾的是並不是所有人及所有的癌症也能從免疫治療中獲益。1672Please respect copyright.PENANAMIqcQAwJmn
1672Please respect copyright.PENANAjSCDKkrfV9
今次的深入淺出,將會為大家講解免疫治療的原理及解釋箇中的好處。1672Please respect copyright.PENANAoLvESyyMlW
1672Please respect copyright.PENANAZz1WmgZgIv
(圖1)正常細胞(Normal Cell)進行繁殖的時候,無可避免會出現DNA變異。我們的細胞雖有著完善的機制可即時修正錯誤,但隨著年紀歲數的增長,修正DNA錯誤的效率亦會相對減低,最終造就DNA出現變異。1672Please respect copyright.PENANAh6OTeCtrGp
1672Please respect copyright.PENANAFEd22JfJYh
1672Please respect copyright.PENANAYB08ZgqvmV
而當細胞DNA出現變異後,我們的免疫細胞T cell會將其視作為外來物,把變異細胞殲滅。1672Please respect copyright.PENANAVGyh8aKueC
1672Please respect copyright.PENANABrV3qRK7HN
可是,若然變異細胞發展出躲避免疫系統的機制,而又累積一定程度的基因變異,便會獲得無驅無束般繁殖的能力,形成腫瘤。1672Please respect copyright.PENANARJDpvYRfgE
1672Please respect copyright.PENANADYdW2INIo3
(圖2)癌細胞躲避免疫系統機制的方法有很多種,較為常見的是PD1(Programmed cell death protein1)系統。1672Please respect copyright.PENANATGVShFQc06
1672Please respect copyright.PENANAt0ZDUjTBOl
1672Please respect copyright.PENANAkzAlCBwMiE
1672Please respect copyright.PENANAVRl4Hnlo4G
我們的T cell會依靠癌細胞與別不同的蛋白質(Neoantigen)來作出辨認,並將變異細胞殲滅。1672Please respect copyright.PENANAlwzRFib6hh
1672Please respect copyright.PENANAvAtamyfEsi
但是若果變異細胞的表面產生名為PDL1的蛋白質,它便能夠與T Cell的PD1作出合併,因此觸發一系列的機制,大幅度銳弱T cell殺滅變異細胞的能力,導致T cell再也不能消滅自己。1672Please respect copyright.PENANAqzjfZJVwuA
1672Please respect copyright.PENANATmOieBNngh
形象化的來說,若果癌細胞穿上「我愛警察」的衣服(PDL1)後,擁有PD1警棍的黑警便會立刻手軟,放生癌細胞離開,讓癌細胞繼續任意妄為。1672Please respect copyright.PENANAxdyQsPe5wQ
1672Please respect copyright.PENANAyK2sxQM4wq
換句話說,癌細胞只要能夠產生PDL1,就能夠逃避T cell的追捕及殺滅;1672Please respect copyright.PENANAC9AININ4Yl
相對上,皮膚癌及肺癌的癌細胞較大機會出現PDL1。1672Please respect copyright.PENANAWJXk9M5Bbm
1672Please respect copyright.PENANAx9B9Hs84tl
1672Please respect copyright.PENANA9GfHmOAQcN
(圖3)既然了解得到PDL1/PD1的關係,那麼對付的方法顯然變得非常簡單,只要把對應的抗體送到體內,阻截PDL1及PD1合併便可。1672Please respect copyright.PENANAF6qV66aLoF
1672Please respect copyright.PENANAfjUrtliOUF
1672Please respect copyright.PENANAqoI7iKHaon
1672Please respect copyright.PENANATDigA4FjHi
以下為現今運用在治療中及臨床研究中的抗體整理。1672Please respect copyright.PENANAeVXRSE0o3P
1672Please respect copyright.PENANAyZ6gGDUITP
阻擋PD1的抗體:1672Please respect copyright.PENANAsm1nmU9Hqx
1.Nivolumab (FDA approved)1672Please respect copyright.PENANAvUI5eC9M2c
2.Pembrolizumab (FDA approved)1672Please respect copyright.PENANAcaSSpCgDJZ
3.Pidilizumab1672Please respect copyright.PENANARdHsmvrEor
4.MEDI-06801672Please respect copyright.PENANA50ukCCY8iT
4.PDR0011672Please respect copyright.PENANAI232Jd5sSn
5.REGN28101672Please respect copyright.PENANAs2GaMpsFKe
1672Please respect copyright.PENANALjTGwGNkPL
阻擋PDL1的抗體:1672Please respect copyright.PENANAuI4I3Gab37
1.Atezolimumab1672Please respect copyright.PENANAozlhvR4XaK
2.Durvalumab1672Please respect copyright.PENANApEE4cqssoH
3.Avelumab1672Please respect copyright.PENANA5Immf1op1u
4.MDX-11051672Please respect copyright.PENANAuCDblGY12v
1672Please respect copyright.PENANAZ6BBbaYu6v
1672Please respect copyright.PENANAhznov2IaOj
簡單來說,就是利用抗體來阻截PD1/PDL1,促使癌細胞無法逃避免疫細胞的追捕,被迫接收免疫細胞的制裁。1672Please respect copyright.PENANAFNf1Hls67b
1672Please respect copyright.PENANAi5D9KJbKo0
1672Please respect copyright.PENANAfWlUsFmlsM
(圖4)為突顯Immunotherapy(免疫系統治療)的好處,我們可以找一個Chemotherapy(化療)的例子作出比較。1672Please respect copyright.PENANAP5NFK4vPgd
1672Please respect copyright.PENANAiP67lLSJCO
1672Please respect copyright.PENANAxWDL31dvD5
針對癌細胞出現X變異,我們便用上針對X變異的化療藥物醫治。1672Please respect copyright.PENANAKEKGa6ZUHQ
1672Please respect copyright.PENANA0fEcD3imiT
在初期,此方法可能會有奇效,但是隨著時間推進,沒有死去的話癌細胞便會發展出不同抗藥機制,導致藥物失效。1672Please respect copyright.PENANAgDg7yoKHBn
1672Please respect copyright.PENANApTMYKM7dyQ
譬如說,X變異變成Y變異,導致只針對X變異的藥物再也沒能針對自己。1672Please respect copyright.PENANARm8FmIgOjv
1672Please respect copyright.PENANAMAuVTT2u2q
又或者,癌細胞會產生蛋白質將藥物帶出細胞外,現今有著不同真實例子顯示出還有各種不同的機制,在這裡不便詳列。1672Please respect copyright.PENANAIjyaQnHKLB
1672Please respect copyright.PENANAmuJBtKs2S0
(圖5)但是,在免疫系統治療方面來說,無論癌細胞如何變異也好,它們始終亦會被T cell界定為外來之物,成為被殲滅的目標。1672Please respect copyright.PENANAx6L0WvQtSC
甚之乎,越多的變異反而會更容易令T cell被認出為外來之物,更易被成為T cell的目標。1672Please respect copyright.PENANAEUSY6qfmEg
1672Please respect copyright.PENANA6XESZit7w3
1672Please respect copyright.PENANAKf5xjGriuL
1672Please respect copyright.PENANAzuZ0QmuSql
在這裡,我們可以看得出免疫治療的精髓所在。1672Please respect copyright.PENANAx5MJJ9JLWl
1672Please respect copyright.PENANA9Zy6btfYkP
免疫治療的方針並不是在針對癌細胞自身,而是針對癌細胞逃避免疫系統細胞的機制。1672Please respect copyright.PENANA2mpkFcsqNo
1672Please respect copyright.PENANAoBGAUWlOjw
在此,我們只是讓免疫系統回復正常運作,糾正它們懂得把癌細胞辨認為外來物,並把外來物消除。1672Please respect copyright.PENANAP3nkQWxzTZ
1672Please respect copyright.PENANAKvPiVJYyVy
這方法根本上沒有額外改動身體的機制,有部份病人可能會出現輕微作嘔感覺,但大部份人士並不會遭受脫髮、食慾不振、手軟腳軟、血球細胞出現問題等等會在化療時候遭受得到的副作用!1672Please respect copyright.PENANAbfQBWowaMN
1672Please respect copyright.PENANAjE5IgL2txi
1672Please respect copyright.PENANAcZWPFkzv2Q
只不過的是,普遍來說一整個免疫治療至少需要美金150,000才能進行,而且若然癌細胞並沒有產生大量PDL1的話,這方法亦不會太過有效。1672Please respect copyright.PENANAbr4iq5E3pN
1672Please respect copyright.PENANAoqKahtWxqh
對此,現時科學家亦研發出不同手段針對這個問題,若然大家對這話題有興趣的話,請正評以及回覆此Post,我會視乎反應寫出下集講解現時免疫治療的最新發展、成果及所面對著的問題。1672Please respect copyright.PENANAyKRA0UQLV2
1672Please respect copyright.PENANA9qBj68AAZ7
希望大家看完這篇文章後,會領略得到免疫治療的原理及與化療手段的根本性分別。1672Please respect copyright.PENANAqz8qRkLky8
1672Please respect copyright.PENANAoDTDvYDAJz
如果想我快啲出文的話,請入去Penana網站科普專欄–薯不揀單俾一個like以及Bookmark,這對我非常之重要。1672Please respect copyright.PENANAckuHuGhJ39
1672Please respect copyright.PENANASQnE34DQdb
Link: https://www.penana.com/story/66244/%E7%A7%91%E6%99%AE%E5%B0%88%E6%AC%84-%E8%96%AF%E4%B8%8D%E6%8F%80%E5%96%AE/toc1672Please respect copyright.PENANAXwiuNjDYVY
1672Please respect copyright.PENANANwack7o8FC
同時亦可以在Penana網站裡按「買一嚿/半嚿薯仔」,以課金的方式推動我繼續搜羅資料寫文,多謝。1672Please respect copyright.PENANAsrzXBrnKPw
1672Please respect copyright.PENANATmBTBjwlDH
Link:1672Please respect copyright.PENANARd4WGtqEvF
https://www.penana.com/user/27349/%E8%96%AF%E4%BB%94%E8%81%9E%E8%8C%B1%E8%8E%89/portfolio1672Please respect copyright.PENANAbrjcUX6ABx
1672Please respect copyright.PENANAz9lvUWTYKY
1672Please respect copyright.PENANAMgDhzKRWNr
有興趣接收科普資訊的話,歡迎follow IG: potatopigtongue。1672Please respect copyright.PENANAA7SJd5MCT7