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」;1674Please respect copyright.PENANAeNNrb2bPRf
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。1674Please respect copyright.PENANAbDbhZ4LYFS
1674Please respect copyright.PENANAJvNXdvVpUe
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。1674Please respect copyright.PENANA9gZWxKSmzJ
1674Please respect copyright.PENANA89LJsObxym
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。1674Please respect copyright.PENANAUjJqLzQWBH
1674Please respect copyright.PENANApx3aRI15mW
(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。1674Please respect copyright.PENANAp1l5kkqQ4o
1674Please respect copyright.PENANA4FDMtNinjp
1674Please respect copyright.PENANAcvD7IrI8f7
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。1674Please respect copyright.PENANAE44tLK43Vt
1674Please respect copyright.PENANAdWZxouXFok
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。1674Please respect copyright.PENANA8PcbyatETZ
1674Please respect copyright.PENANA87qofO1KzE
(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。1674Please respect copyright.PENANAYeKhtqwrQc
1674Please respect copyright.PENANAlsgdUzhtVH
1674Please respect copyright.PENANAgcuMzTIvnm
1674Please respect copyright.PENANAANrx192AZE
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。1674Please respect copyright.PENANAdmT85kdK2o
1674Please respect copyright.PENANAGIJk3FhPop
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。1674Please respect copyright.PENANACQZnLGy7eJ
1674Please respect copyright.PENANA0wCSJ7F8fT
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。1674Please respect copyright.PENANALjPgoBoABy
1674Please respect copyright.PENANAR0e3FI1EDp
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;1674Please respect copyright.PENANAJ0WX1sh7JA
相對上,皮膚癌及肺癌的癌細胞較大機會出現PDL1。1674Please respect copyright.PENANAqJZW4vQn40
1674Please respect copyright.PENANAqxzOslWEM6
1674Please respect copyright.PENANATc3RJpDaKF
(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。1674Please respect copyright.PENANAiHfbsE4XBf
1674Please respect copyright.PENANAh6DmLmu62z
1674Please respect copyright.PENANA82S0QgpNXA
1674Please respect copyright.PENANAcJviNNz0cj
以下為現今運用在治療中及臨床研究中的抗體整理。1674Please respect copyright.PENANAN3AAMpWrt2
1674Please respect copyright.PENANAmfaJhZhlC5
阻擋PD1的抗體:1674Please respect copyright.PENANAvJSB4sxxKD
1.Nivolumab (FDA approved)1674Please respect copyright.PENANA7mKC0aGInz
2.Pembrolizumab (FDA approved)1674Please respect copyright.PENANAfdyJgKriTB
3.Pidilizumab1674Please respect copyright.PENANAMatydezADC
4.MEDI-06801674Please respect copyright.PENANADZ9Ha0butQ
4.PDR0011674Please respect copyright.PENANANLGA1q2ioo
5.REGN28101674Please respect copyright.PENANAoPt6DdzN45
1674Please respect copyright.PENANAn3pSgm7KCj
阻擋PDL1的抗體:1674Please respect copyright.PENANAgUpiPSWrMy
1.Atezolimumab1674Please respect copyright.PENANASJJe6AZOmQ
2.Durvalumab1674Please respect copyright.PENANAU1ycQyufWa
3.Avelumab1674Please respect copyright.PENANAuRUxnPdzMb
4.MDX-11051674Please respect copyright.PENANAt5TD2zkstU
1674Please respect copyright.PENANAmFccsU8m1j
1674Please respect copyright.PENANAzzdB9KbCVl
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。1674Please respect copyright.PENANAmDVfbzSeQj
1674Please respect copyright.PENANAnScn0Pwld3
1674Please respect copyright.PENANA6fFcyNIko6
(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。1674Please respect copyright.PENANAsYy0sLnJkJ
1674Please respect copyright.PENANAOLoC0U59my
1674Please respect copyright.PENANAlzA3seO5Ha
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。1674Please respect copyright.PENANAEMDSoLsplk
1674Please respect copyright.PENANArsxkf7eahJ
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。1674Please respect copyright.PENANASZd2gGdFx0
1674Please respect copyright.PENANA11H4Jv3LOR
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。1674Please respect copyright.PENANAGGjKyqFOf6
1674Please respect copyright.PENANAvpRNnR3QLs
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。1674Please respect copyright.PENANAT6wulhSy0j
1674Please respect copyright.PENANAy66nKf7QyL
(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。1674Please respect copyright.PENANA7bBha2hx8k
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。1674Please respect copyright.PENANAWu6OgElRmK
1674Please respect copyright.PENANA0rv14mJx64
1674Please respect copyright.PENANAhVA146Tfv0
1674Please respect copyright.PENANACHvuXoPF8E
在這裡,我們可以看得出免疫治療的精髓所在。1674Please respect copyright.PENANAJYj2eqC8w3
1674Please respect copyright.PENANAX7XCtVXUWF
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。1674Please respect copyright.PENANAWzaeM2rwuT
1674Please respect copyright.PENANATfn1o99ks2
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。1674Please respect copyright.PENANAPBu0ALKWPC
1674Please respect copyright.PENANA1U7c0Bpx6Q
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!1674Please respect copyright.PENANAbfMrDJ4zmS
1674Please respect copyright.PENANAyFyrM01Uqb
1674Please respect copyright.PENANAMSdzRMfeaY
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。1674Please respect copyright.PENANAAZwAfbR8k2
1674Please respect copyright.PENANADW2v4Cv5cU
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。1674Please respect copyright.PENANArXeMin6Chl
1674Please respect copyright.PENANAyy657zvGWJ
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。1674Please respect copyright.PENANA1LEezGC26q
1674Please respect copyright.PENANABAwaNjD8kx
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。1674Please respect copyright.PENANA8VrK9tVTNc
1674Please respect copyright.PENANAFPcndfin3y
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/toc1674Please respect copyright.PENANA3WFm1XZEXN
1674Please respect copyright.PENANApM120zAk2u
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。1674Please respect copyright.PENANAqSHPeALPsn
1674Please respect copyright.PENANAXmsjCsPkJi
Link:1674Please respect copyright.PENANAa2UY17hgmd
https://www.penana.com/user/27349/%E8%96%AF%E4%BB%94%E8%81%9E%E8%8C%B1%E8%8E%89/portfolio1674Please respect copyright.PENANAEkPIVpISDl
1674Please respect copyright.PENANA1WlNfU5aBi
1674Please respect copyright.PENANAfJlbtIpCVO
有興趣接收科普資訊的話,歡迎follow IG: potatopigtongue。1674Please respect copyright.PENANAq6jf9KzjJS