科普專欄–薯不揀單 - 深入淺出–免疫治療(Immunotherapy)手段醫治癌症

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」;2395Please respect copyright.ＰＥＮＡＮＡxlq1B4QhqQ
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。2395Please respect copyright.ＰＥＮＡＮＡSY3k37WGxp
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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。2395Please respect copyright.ＰＥＮＡＮＡ4kl3pIAiI0
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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。2395Please respect copyright.ＰＥＮＡＮＡiaGMZ30dSD
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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。2395Please respect copyright.ＰＥＮＡＮＡJAehWHXTlt
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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。2395Please respect copyright.ＰＥＮＡＮＡnuCPWPZLoI
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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。2395Please respect copyright.ＰＥＮＡＮＡEqfezGeydT
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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。2395Please respect copyright.ＰＥＮＡＮＡe5C2KhqO8p
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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。2395Please respect copyright.ＰＥＮＡＮＡBn4U7otWjG
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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。2395Please respect copyright.ＰＥＮＡＮＡn6HjFIgfqW
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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。2395Please respect copyright.ＰＥＮＡＮＡzHAjTQZ910
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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;2395Please respect copyright.ＰＥＮＡＮＡYPywZztlqN
相對上，皮膚癌及肺癌的癌細胞較大機會出現PDL1。2395Please respect copyright.ＰＥＮＡＮＡlDmRvplybc
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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。2395Please respect copyright.ＰＥＮＡＮＡtmZaYiOrTb
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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。2395Please respect copyright.ＰＥＮＡＮＡcazDKeNjgk
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阻擋PD1的抗體:2395Please respect copyright.ＰＥＮＡＮＡ9Bv1DWetOY
1.Nivolumab (FDA approved)2395Please respect copyright.ＰＥＮＡＮＡfm3mvJqSPd
2.Pembrolizumab (FDA approved)2395Please respect copyright.ＰＥＮＡＮＡXSOw5fTVMm
3.Pidilizumab2395Please respect copyright.ＰＥＮＡＮＡpP02W2tQ0d
4.MEDI-06802395Please respect copyright.ＰＥＮＡＮＡn62kDo4cTW
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5.REGN28102395Please respect copyright.ＰＥＮＡＮＡ5mT8fA5zPg
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阻擋PDL1的抗體:2395Please respect copyright.ＰＥＮＡＮＡFsb3gMLDwC
1.Atezolimumab2395Please respect copyright.ＰＥＮＡＮＡu3cNHzonFX
2.Durvalumab2395Please respect copyright.ＰＥＮＡＮＡjzAu4O3ldA
3.Avelumab2395Please respect copyright.ＰＥＮＡＮＡ8Qd166dIo0
4.MDX-11052395Please respect copyright.ＰＥＮＡＮＡNvLUvuY3Ij
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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。2395Please respect copyright.ＰＥＮＡＮＡHP08sQaRNf
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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。2395Please respect copyright.ＰＥＮＡＮＡxGIpxADs6w
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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。2395Please respect copyright.ＰＥＮＡＮＡCxDj8VSI9H
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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。2395Please respect copyright.ＰＥＮＡＮＡ14LfIhiukD
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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。2395Please respect copyright.ＰＥＮＡＮＡD6gBAlUhNG
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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。2395Please respect copyright.ＰＥＮＡＮＡ4eCXAasqJx
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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。2395Please respect copyright.ＰＥＮＡＮＡ9mptWG4CGM
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。2395Please respect copyright.ＰＥＮＡＮＡdz4YTpVED2
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在這裡，我們可以看得出免疫治療的精髓所在。2395Please respect copyright.ＰＥＮＡＮＡ3gYfWuF4ER
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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。2395Please respect copyright.ＰＥＮＡＮＡxdsYLTxkUz
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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。2395Please respect copyright.ＰＥＮＡＮＡwQ853Z4eXY
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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！2395Please respect copyright.ＰＥＮＡＮＡHSl3Neapyd
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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。2395Please respect copyright.ＰＥＮＡＮＡmjqvHBv5YD
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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。2395Please respect copyright.ＰＥＮＡＮＡxlHcTW9wlk
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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。2395Please respect copyright.ＰＥＮＡＮＡrksIBeMxQh
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