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」;2009Please respect copyright.ＰＥＮＡＮＡBbfm2SGDr8
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。2009Please respect copyright.ＰＥＮＡＮＡQGyGgVQrkF
2009Please respect copyright.ＰＥＮＡＮＡV5jWWY1b4K
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。2009Please respect copyright.ＰＥＮＡＮＡbs7lnsKy3O
2009Please respect copyright.ＰＥＮＡＮＡoaZghNJPA1
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。2009Please respect copyright.ＰＥＮＡＮＡWegteAbWDA
2009Please respect copyright.ＰＥＮＡＮＡuJpHBAdh5A
（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。2009Please respect copyright.ＰＥＮＡＮＡ6jf5WrI5Ta
2009Please respect copyright.ＰＥＮＡＮＡAlGYrImmrx
2009Please respect copyright.ＰＥＮＡＮＡY8i4zJX7xW
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。2009Please respect copyright.ＰＥＮＡＮＡrfcXm6WyyG
2009Please respect copyright.ＰＥＮＡＮＡd6iJhkiVka
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。2009Please respect copyright.ＰＥＮＡＮＡ9pYYsPjLIl
2009Please respect copyright.ＰＥＮＡＮＡO4UcNV3das
（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。2009Please respect copyright.ＰＥＮＡＮＡI3R8hHl7HY
2009Please respect copyright.ＰＥＮＡＮＡp2k8bDM7O7
2009Please respect copyright.ＰＥＮＡＮＡJHPzOcossU
2009Please respect copyright.ＰＥＮＡＮＡkX3JDZEvTH
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。2009Please respect copyright.ＰＥＮＡＮＡsQmi9Plppw
2009Please respect copyright.ＰＥＮＡＮＡovxhu4JwuS
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。2009Please respect copyright.ＰＥＮＡＮＡXbnBmyeKeC
2009Please respect copyright.ＰＥＮＡＮＡ88sSsjpBSu
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。2009Please respect copyright.ＰＥＮＡＮＡC7glVyPsGJ
2009Please respect copyright.ＰＥＮＡＮＡnBNZtsAZde
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;2009Please respect copyright.ＰＥＮＡＮＡO9L4hODByJ
相對上，皮膚癌及肺癌的癌細胞較大機會出現PDL1。2009Please respect copyright.ＰＥＮＡＮＡStJ5cRDMcW
2009Please respect copyright.ＰＥＮＡＮＡYBMzcV2SaS
2009Please respect copyright.ＰＥＮＡＮＡDxUSYfTID5
（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。2009Please respect copyright.ＰＥＮＡＮＡvpvlPrBGPC
2009Please respect copyright.ＰＥＮＡＮＡi9pwQzeh3h
2009Please respect copyright.ＰＥＮＡＮＡUcF1HAfkyz
2009Please respect copyright.ＰＥＮＡＮＡ4U0l3D30ou
以下為現今運用在治療中及臨床研究中的抗體整理。2009Please respect copyright.ＰＥＮＡＮＡUJIQ5VSGuL
2009Please respect copyright.ＰＥＮＡＮＡ6KMuWX4mXu
阻擋PD1的抗體:2009Please respect copyright.ＰＥＮＡＮＡ7JmVuKYFa9
1.Nivolumab (FDA approved)2009Please respect copyright.ＰＥＮＡＮＡ5YRHeVUsSX
2.Pembrolizumab (FDA approved)2009Please respect copyright.ＰＥＮＡＮＡDqoRfr4zH5
3.Pidilizumab2009Please respect copyright.ＰＥＮＡＮＡOIgCiUYiLJ
4.MEDI-06802009Please respect copyright.ＰＥＮＡＮＡNo4JHD3zxY
4.PDR0012009Please respect copyright.ＰＥＮＡＮＡ9Z1DjPjFts
5.REGN28102009Please respect copyright.ＰＥＮＡＮＡ7FvsdYF1Aq
2009Please respect copyright.ＰＥＮＡＮＡ3GQY92j84C
阻擋PDL1的抗體:2009Please respect copyright.ＰＥＮＡＮＡY4rt7dKIjT
1.Atezolimumab2009Please respect copyright.ＰＥＮＡＮＡhXmE3GU2E9
2.Durvalumab2009Please respect copyright.ＰＥＮＡＮＡrikNRv6lJH
3.Avelumab2009Please respect copyright.ＰＥＮＡＮＡKcfdq4RAn2
4.MDX-11052009Please respect copyright.ＰＥＮＡＮＡ6AEf6DqVsR
2009Please respect copyright.ＰＥＮＡＮＡVYfjQf23z2
2009Please respect copyright.ＰＥＮＡＮＡRdW7kjbSLf
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。2009Please respect copyright.ＰＥＮＡＮＡbaQLU9jL3r
2009Please respect copyright.ＰＥＮＡＮＡxxw7eTdOCa
2009Please respect copyright.ＰＥＮＡＮＡg1Dj7RyoXr
（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。2009Please respect copyright.ＰＥＮＡＮＡkQzopakSHn
2009Please respect copyright.ＰＥＮＡＮＡKlQIC4kVMx
2009Please respect copyright.ＰＥＮＡＮＡDoybf2e8Vb
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。2009Please respect copyright.ＰＥＮＡＮＡgy0d7u9KVs
2009Please respect copyright.ＰＥＮＡＮＡJwnN8HSLgW
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。2009Please respect copyright.ＰＥＮＡＮＡL8BqxF2qMT
2009Please respect copyright.ＰＥＮＡＮＡ5n5ZCwOIic
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。2009Please respect copyright.ＰＥＮＡＮＡrpkngv8abr
2009Please respect copyright.ＰＥＮＡＮＡsxoh0CWH5U
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。2009Please respect copyright.ＰＥＮＡＮＡOgV2vScfh1
2009Please respect copyright.ＰＥＮＡＮＡaRwLj4fp8K
（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。2009Please respect copyright.ＰＥＮＡＮＡmNb5QY62XL
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。2009Please respect copyright.ＰＥＮＡＮＡOaMMkDxZFI
2009Please respect copyright.ＰＥＮＡＮＡFjre5s51w0
2009Please respect copyright.ＰＥＮＡＮＡfZLE58nWc5
2009Please respect copyright.ＰＥＮＡＮＡecZKmabGC1
在這裡，我們可以看得出免疫治療的精髓所在。2009Please respect copyright.ＰＥＮＡＮＡlbVdyp1mst
2009Please respect copyright.ＰＥＮＡＮＡuVGEol2N8u
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。2009Please respect copyright.ＰＥＮＡＮＡNNd2rPjnIO
2009Please respect copyright.ＰＥＮＡＮＡVuvJYcBhKF
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。2009Please respect copyright.ＰＥＮＡＮＡfy3LomFbw3
2009Please respect copyright.ＰＥＮＡＮＡx0rJ1asFcZ
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！2009Please respect copyright.ＰＥＮＡＮＡP8Jy2Ftnh7
2009Please respect copyright.ＰＥＮＡＮＡpxdy78DAd2
2009Please respect copyright.ＰＥＮＡＮＡXWYwDxzwTO
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。2009Please respect copyright.ＰＥＮＡＮＡ04LD27sDSF
2009Please respect copyright.ＰＥＮＡＮＡHthomlSg0S
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。2009Please respect copyright.ＰＥＮＡＮＡRvmRfKQr8Y
2009Please respect copyright.ＰＥＮＡＮＡonl7r2dZ5s
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。2009Please respect copyright.ＰＥＮＡＮＡBppNOF1s8O
2009Please respect copyright.ＰＥＮＡＮＡQKHCdKCGQH
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。2009Please respect copyright.ＰＥＮＡＮＡNiG7JBDyrw
2009Please respect copyright.ＰＥＮＡＮＡcOAWgmBE9M
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/toc2009Please respect copyright.ＰＥＮＡＮＡdmEfNd7Ajo
2009Please respect copyright.ＰＥＮＡＮＡdtcd3rqkwU
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。2009Please respect copyright.ＰＥＮＡＮＡoEsXtSoUvi
2009Please respect copyright.ＰＥＮＡＮＡQ912tIkzo6
Link:2009Please respect copyright.ＰＥＮＡＮＡesRM8hcGc0
https://www.penana.com/user/27349/%E8%96%AF%E4%BB%94%E8%81%9E%E8%8C%B1%E8%8E%89/portfolio2009Please respect copyright.ＰＥＮＡＮＡqAcywCV6RH
2009Please respect copyright.ＰＥＮＡＮＡtNzsPXzKuU
2009Please respect copyright.ＰＥＮＡＮＡ4Kii4X6JRh
有興趣接收科普資訊的話，歡迎follow IG: potatopigtongue。2009Please respect copyright.ＰＥＮＡＮＡ2c9w5ss4zi