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」;1626Please respect copyright.PENANAugYOegJaoX
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。1626Please respect copyright.PENANA0Zrg0Z8Fy7
1626Please respect copyright.PENANAfbpmUqOBog
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。1626Please respect copyright.PENANAnhSYgCKRWS
1626Please respect copyright.PENANAkkAfslMtdr
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。1626Please respect copyright.PENANAyLCkM54K7v
1626Please respect copyright.PENANArZhzitY7gR
(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。1626Please respect copyright.PENANA5JxUaIXyMc
1626Please respect copyright.PENANANpkXjEFtE9
1626Please respect copyright.PENANAhiyEBHInnW
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。1626Please respect copyright.PENANAanyoMKLLEI
1626Please respect copyright.PENANAwLbeQn00rm
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。1626Please respect copyright.PENANAagsyq4QP65
1626Please respect copyright.PENANA6XNJK4JYAY
(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。1626Please respect copyright.PENANA2eZGLAdjDH
1626Please respect copyright.PENANA6f2p4w7YVJ
1626Please respect copyright.PENANAKpimh1E0rk
1626Please respect copyright.PENANAGi5mewMTkx
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。1626Please respect copyright.PENANANCDsjzrsNt
1626Please respect copyright.PENANAkQbTTXs9oO
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。1626Please respect copyright.PENANATOIbyCwGQT
1626Please respect copyright.PENANAl4Ze9rl8Sv
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。1626Please respect copyright.PENANAyMZJioBXXL
1626Please respect copyright.PENANABj15ysj21L
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;1626Please respect copyright.PENANAbOn9zfHpHI
相對上,皮膚癌及肺癌的癌細胞較大機會出現PDL1。1626Please respect copyright.PENANAq9Pu0DLIKc
1626Please respect copyright.PENANAMAJYp87JLC
1626Please respect copyright.PENANA0JyCRQT5tK
(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。1626Please respect copyright.PENANAjNs8yVjf0K
1626Please respect copyright.PENANAhub1vpcF16
1626Please respect copyright.PENANA9HU03bFqUt
1626Please respect copyright.PENANAF76oGiH1Mg
以下為現今運用在治療中及臨床研究中的抗體整理。1626Please respect copyright.PENANA8uIaB87Nuq
1626Please respect copyright.PENANAxRKt588oPL
阻擋PD1的抗體:1626Please respect copyright.PENANAOwqJrtr01w
1.Nivolumab (FDA approved)1626Please respect copyright.PENANAawxj8GHGnq
2.Pembrolizumab (FDA approved)1626Please respect copyright.PENANAbkmZ3ATPO7
3.Pidilizumab1626Please respect copyright.PENANAWtpV93Pe6r
4.MEDI-06801626Please respect copyright.PENANAaYZL69rNhv
4.PDR0011626Please respect copyright.PENANAEBWjjWqbWI
5.REGN28101626Please respect copyright.PENANA79C7SXIfrz
1626Please respect copyright.PENANAL0VyoQcSQ9
阻擋PDL1的抗體:1626Please respect copyright.PENANATKmjHiDkl4
1.Atezolimumab1626Please respect copyright.PENANADIZzsy6rtI
2.Durvalumab1626Please respect copyright.PENANATtiV6u5e79
3.Avelumab1626Please respect copyright.PENANASWShAinBHR
4.MDX-11051626Please respect copyright.PENANAfUYEigNQ3R
1626Please respect copyright.PENANAVEofz1Y8Ea
1626Please respect copyright.PENANAqC6DIfmSaq
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。1626Please respect copyright.PENANA2NSpseOQ1D
1626Please respect copyright.PENANAMy4TWWHjUe
1626Please respect copyright.PENANAhl8TexQd6e
(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。1626Please respect copyright.PENANAEwf8eL6TvV
1626Please respect copyright.PENANAc1pZI4ymlB
1626Please respect copyright.PENANARh9Lrf57sq
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。1626Please respect copyright.PENANAH9zgII0lmR
1626Please respect copyright.PENANAUQifwTZqBI
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。1626Please respect copyright.PENANAd9xvQKRFVp
1626Please respect copyright.PENANAUT5oYHP0wK
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。1626Please respect copyright.PENANAwzRmPcm7Bi
1626Please respect copyright.PENANAKStG8vXUTh
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。1626Please respect copyright.PENANA22FCdh5Q4j
1626Please respect copyright.PENANAcCSlLVi9Ec
(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。1626Please respect copyright.PENANA8TD1eD4Qnl
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。1626Please respect copyright.PENANAMlUIL2lIMg
1626Please respect copyright.PENANAbfWQNi0jKA
1626Please respect copyright.PENANAufJWtkapz8
1626Please respect copyright.PENANAJRrgdZVke1
在這裡,我們可以看得出免疫治療的精髓所在。1626Please respect copyright.PENANAqMhdCytVwN
1626Please respect copyright.PENANAkEyBRkRQOi
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。1626Please respect copyright.PENANAK5wtqwTSoG
1626Please respect copyright.PENANAB8YhnKdxT9
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。1626Please respect copyright.PENANAoDl4cvLjRc
1626Please respect copyright.PENANApqr3DXds77
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!1626Please respect copyright.PENANACAMVHVWuFZ
1626Please respect copyright.PENANAUiUpnytyjS
1626Please respect copyright.PENANAnyGDhxc9tD
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。1626Please respect copyright.PENANALd9vdpbQ3I
1626Please respect copyright.PENANAJ9uusQDJnK
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。1626Please respect copyright.PENANA9gKZweJADc
1626Please respect copyright.PENANAtrFJn7XICy
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。1626Please respect copyright.PENANAQ3x9K1ABcQ
1626Please respect copyright.PENANABqz9i0VwZP
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。1626Please respect copyright.PENANAJBubFdn6j4
1626Please respect copyright.PENANAlifl55sQSD
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/toc1626Please respect copyright.PENANAJdYpUhvBI3
1626Please respect copyright.PENANAbkQ1AUpJrn
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。1626Please respect copyright.PENANAHryqCW8XXU
1626Please respect copyright.PENANAU3mkL2sU8L
Link:1626Please respect copyright.PENANA8jghZlTU63
https://www.penana.com/user/27349/%E8%96%AF%E4%BB%94%E8%81%9E%E8%8C%B1%E8%8E%89/portfolio1626Please respect copyright.PENANAz2isAbHHT1
1626Please respect copyright.PENANAnmFpwRlbyD
1626Please respect copyright.PENANAT2fxHmDUeI
有興趣接收科普資訊的話,歡迎follow IG: potatopigtongue。1626Please respect copyright.PENANA5bwf26udKa