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」;1665Please respect copyright.PENANAT02Zc0PBhd
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。1665Please respect copyright.PENANAoc6lryLv32
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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。1665Please respect copyright.PENANAyIJ3IRiyoH
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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。1665Please respect copyright.PENANAUDNbdkBAzt
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(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。1665Please respect copyright.PENANAnZeZkmjsS2
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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。1665Please respect copyright.PENANA8qOUYZ9eL7
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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。1665Please respect copyright.PENANADVC0nJIEuF
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(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。1665Please respect copyright.PENANA1j3peWFFlY
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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。1665Please respect copyright.PENANAKYjeJ7praZ
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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。1665Please respect copyright.PENANAWRzbWILP77
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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。1665Please respect copyright.PENANAlbB3ls3Smy
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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;1665Please respect copyright.PENANAL8PRAiD8Iu
相對上,皮膚癌及肺癌的癌細胞較大機會出現PDL1。1665Please respect copyright.PENANARZY1YAldUC
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(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。1665Please respect copyright.PENANAHgMkiJ56iF
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以下為現今運用在治療中及臨床研究中的抗體整理。1665Please respect copyright.PENANA5BKN7XgI1O
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阻擋PD1的抗體:1665Please respect copyright.PENANAKAIYFvbWAb
1.Nivolumab (FDA approved)1665Please respect copyright.PENANA47bx4eBq0U
2.Pembrolizumab (FDA approved)1665Please respect copyright.PENANAaqRUvgp6C4
3.Pidilizumab1665Please respect copyright.PENANAh3o3wgOy8f
4.MEDI-06801665Please respect copyright.PENANAxjRnX3NnDN
4.PDR0011665Please respect copyright.PENANAULDtp3UDyt
5.REGN28101665Please respect copyright.PENANANHhebwmynk
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阻擋PDL1的抗體:1665Please respect copyright.PENANAlde0s9XLr5
1.Atezolimumab1665Please respect copyright.PENANArrn2Sj2ZaG
2.Durvalumab1665Please respect copyright.PENANAQp9YkpgE3B
3.Avelumab1665Please respect copyright.PENANAubtUjadsdg
4.MDX-11051665Please respect copyright.PENANA4yUm9JnjTd
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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。1665Please respect copyright.PENANAcUmO86mT4F
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(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。1665Please respect copyright.PENANAM8mvPyGivD
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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。1665Please respect copyright.PENANALAKwIipmEm
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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。1665Please respect copyright.PENANA62AkeDvIYp
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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。1665Please respect copyright.PENANARUnFsAW0bJ
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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。1665Please respect copyright.PENANAjDeJv8j5vW
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(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。1665Please respect copyright.PENANAvpCICO8zGT
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。1665Please respect copyright.PENANAai06qV0ohP
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在這裡,我們可以看得出免疫治療的精髓所在。1665Please respect copyright.PENANAdiuoghPqBj
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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。1665Please respect copyright.PENANARgU6ourmBs
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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。1665Please respect copyright.PENANAmQRaMKLZTW
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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!1665Please respect copyright.PENANAcSIpREBbvL
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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。1665Please respect copyright.PENANAq0bPMlEb92
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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。1665Please respect copyright.PENANASOr9BJ3YBy
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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。1665Please respect copyright.PENANA5uX4dT8VUd
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