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Kansarka iyo Cilmi-baarista COVID: Doorka Cytokines

Written by Linda S. Hohnholz

Ka dib khudbadii furitaanka ee dhiirigelinta leh, "Aragtida mustaqbalka ee Immunotherapy Kansarka," oo ay bixiso Nobel Prize iyo Tang Prize laureate Prof. Tasuku Honjo ee 14th Asia Pacific Federation of Pharmacologist (APFP) November 26, 2020 Tang Prize Laureate's Lecture for Biopharmaceutical Sayniska, oo ay si wadajir ah u abaabuleen Tang Prize Foundation iyo Society Pharmacological Society ee Taiwan, ayaa ka dhacay 14-aad APFP 1:30 pm (GMT+8) ee Noofambar 27.

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Waxaa iska kaashaday Dr. Wen-Chang Chang, oo ah gudoomiyaha guddiga maamulka ee jaamacadda Taipei Medical, iyo Dr. Yun Yen, oo ah gudoomiyaha borofisar ka ah jaamacadda Taipei Medical University, fadhigan gaarka ah waxaa soo bandhigay muxaadarooyin ay bixiyeen saddex ku guulaystey 2020 Tang Prize ee Sayniska Biopharmaceutical , Drs. Charles Dinarello, Marc Feldmann, iyo Tadamitsu Kishimoto, iyagoo bixinaya macluumaad qiimo leh oo ku saabsan doorka cytokines-ka ee caabuqa iyo cudurka COVID-19 iyo sidoo kale daawaynta suurtagalka ah.

Muxaadaradii ugu horeysay ee Dr. Dinarello, oo cinwaankeedu yahay "Interleukin-1: Dhexdhexaadiyaha Ra'iisul Wasaaraha ee Nidaamka iyo Caabuqa Maxalliga," waxay ku bilaabatay nadiifinta pryogen leukocytic ee unugyada dhiiga cad ee bini'aadamka 1971. Kadib waxay ku qaadatay lix sano si uu u aqoonsado laba qandho- soo saarida molecules, oo markii dambe loo magacaabay IL-1α iyo IL-1β. 1977, natiijooyinka cilmi-baarista waxaa lagu daabacay Tilaabooyinka Akademiyada Qaranka ee Sayniska, iyo Dr. Dinarello, "taasi waxay ahayd tallaabo muhiim ah taariikhda bayoolajiga cytokine," sababtoo ah dad badan oo ku jira sayniska nolosha ayaa lagu dhiirigeliyay baro saamaynta habka difaaca jidhku ku leeyahay physiology-ga aadanaha. Natiijo ahaan, bayooloojiyada cytokine ayaa si degdeg ah u fiday. Waxa kale oo uu ka hadlay sida ka dib tijaabadii hore ee bini'aadamka, "taariikhda cytokines ee loo isticmaalo daawaynta si weyn ayaa isu beddeshay," diiradda ayaa loo wareejiyay "la joojiyo cytokines, sida IL-1, sida TNF, sida IL- 6.” Si loo caawiyo dhagaystayaashu inay fahmaan shabakada adag ee ay ka kooban yihiin molecules pro-inflammatory ee qoyska IL-1, Dr. Dinarello wuxuu faahfaahiyay wareejinta calaamadaha xubnaha qoyska IL-1, sifooyinkooda pro- iyo ka-hortagga bararka, iyo calaamadaha cudurro kala duwan oo barar ah, si loo fududeeyo daawadayaasha si ay si sax ah u fahmaan qeybtii labaad ee muxaadarada taas oo udub dhexaad u ahayd "codsiga caafimaad ee xannibaadda Il-1." Wax-soo-saarka xad-dhaafka ah ee IL-1, sida Dr. Dinarello uu xusay, waa sababta caadiga ah ee cudurro badan. IL-1Ra, dhanka kale, waxay joojin kartaa Il-1αandβ, waxayna xannibi kartaa calaamadda IL-1R. Anakinra, IL-1Ra bini'aadam ah oo dib u habeyn ah ayaa la soo saaray. Waxaa loo isticmaalaa in lagu daweeyo rheumatoid arthritis-ka waxayna sidoo kale ka hortagi kartaa cilladaha glycemic ee nooca 2 ee sonkorowga. Waxaa intaa dheer, canakinumab, anti-IL-1βmonoclonal antibody si guul leh u soo saaray Novartis, ayaa lagu ansixiyay cudurro kala duwan, oo ka soo jeeda cudurrada aan caadiga ahayn ee la iska dhaxlo, cudurrada rheumatic, autoimmune iyo cudurrada bararka, cudurada wadnaha iyo xididdada. Warka ugu xiisaha badan ee ku lug leh canakinumab waa tijaabada kiliinikada, CANTOS, taas oo si lama filaan ah u cadaysay in canakinumab ay door muhiim ah ku leedahay daaweynta kansarka. Sidaa darteed, Dr. Dinarello wuxuu aaminsan yahay in xannibaadda IL-1 ay keeni karto waaberiga daawaynta cusub ee kansarka.

Hadlaha labaad, Dr. Feldmann, wuxuu wadaagay aragtidiisa ku saabsan "Turjumaadda Molecular Insights ee Autoimmunity oo loo beddelo Daaweynta Waxtarka leh." Muhiimadda qeybtii hore ee muxaadaradiisa waxay ahayd sida uu u ogaaday in anti-TNF ay waxtar u yeelan karto daaweynta rheumatoid arthritis-ka. Maareynta qiyaasaha sare ama kuwa hooseeya ee dawadan waxay xannibi kartaa TNF iyada oo sidoo kale si degdeg ah u yareyneysa wax soo saarka dhexdhexaadiyeyaasha kale ee bararka. Tijaabooyinkoodii hore, Dr. Feldmann iyo kooxdiisu waxay muujiyeen in ku dhawaad ​​50% dadka qaba rheumatoid arthritis-ku ay ka jawaabeen daawaynta isku dhafka ah iyagoo isticmaalaya anti-TNF iyo daawada kansarka ee methotrexate. Taasi waxay u horseeday inuu rumaysto in "Waxaan heysanaa waddo dheer oo aan mari karno ka hor inta aan bukaan kasta la daaweyn." Intii lagu jiray qeybtii labaad ee hadalka, Dr. Feldmann wuxuu nagu wargeliyay in "TNF ay tahay mid aan caadi ahayn oo aan caadi ahayn, sababtoo ah waxay leedahay laba bartilmaameed oo kala duwan: TNF receptor-1 (TNFR1), kaas oo keena caabuqa, iyo TNF reseptor 2, kaas oo sameeya wax aad u badan. lid ku ah. Markaa haddii aad xannibto dhammaan TNF, waxaad xannibaysaa daawadayaasha. Waxaad xannibaysaa bararka, laakiin sidoo kale waxaad ka hortagtaa isku dayga jidhku ku doonayo inuu hoos u dhigo bararka." Sidaa darteed, isaga iyo asxaabtiisu waxay ku jiraan "habka soo saarista qalabka" waxayna horey u xannibeen TNFR1 iyada oo aan isbeddelin shaqada unugyada T-da ee nidaamsan. Intaa waxaa dheer, Dr. Feldmann wuxuu xusay awoodda ka-hortagga TNF si wax looga qabto baahiyo caafimaad oo badan oo aan la daboolin, sida daaweynta fibrosis ee gacanta iyada oo la isku duro anti-TNF calaacalaha. Si kastaba ha ahaatee, wuxuu tilmaamay labada faa'iido darro ee ka-hortagga TNF-da ee uu markii ugu horreysay sameeyay: waxay ahayd mid kharash-ma-mnuuc ah iyo "waxay ahayd daawo la isku duro." Haddaba, in la sameeyo "daawooyin ka jaban oo afka laga keeno" waxay faa'iido weyn u keenaysaa bulshada. Muxaadarada oo dhan, Dr. Feldmann waxa uu waday dad badan oo uu la shaqayn jiray ama ay iska kaashanayaan mashaariic iyo tijaabooyin kala duwan, isaga oo isku dayay in uu guriga u wado fariinta ah in waxa uu ka bartay waaya-aragnimadan ay tahay "sida si wax ku ool ah ula shaqeeyo dadka kale" si loo hubiyo horumarka joogtada ah ee cilmi-baaristooda. Waxay ahayd astaanta xirfaddiisa inuu helo "dad karti leh oo lala shaqeeyo," iyo, "si wada jir ah," si uu u gaaro wax ka badan "inta aan keligeen kari karno."

Isagoo soo jeedinaya muxaadarada saddexaad ee mowduuca "Interleukin-6: Laga soo bilaabo Arthritis ilaa CAR-T iyo COVID-19," Dr. Kishimoto wuxuu soo jiitay dareenka daawadayaasha sida IL-6 loo helay, sababta IL-6 u tahay molecule pleiotropic, iyo sababta IL-6 "waxay mas'uul ka tahay soosaarka antibody-ka iyo sidoo kale kicinta caabuqa." Waxa kale oo uu iftiimiyay saamaynta IL-6 ee cudurrada difaaca jirka iyo sida IL-6 ay u kicin karto duufaannada cytokine. Bilowgii hadalkiisa, Dr. Kistimoto wuxuu caddeeyay in soo-saarka xad-dhaafka ah ee IL-6 uu ogaaday inuu la xiriiro cudurro badan, sida myxoma wadnaha, cudurka Castleman, rheumatoid arthritis-ka, iyo bilawga hab-dhiska ee idiopathic arthritis-ka (JIA). Si wax looga qabto jawaabaha bararka ee ay kicisay wax-soo-saarka xad-dhaafka ah ee IL-6, Dr. Kishimoto iyo kooxdiisu waxay isku dayeen inay daweeyaan bukaannada iyagoo xannibaya calaamadaha IL-6. Ka dib, tocilizumab, oo ah dib-u-habeyn bini'aadminimo anti-IL-6 receptor monoclonal antibody, ayaa si guul leh loo sameeyay waxaana loo oggolaaday isticmaalka in ka badan 100 waddan oo loogu talagalay daaweynta rheumatoid arthritis-ka iyo JIA. Marka la eego sida wax-soo-saarka IL-6 loo xakameeyo iyo sababta IL-6 wax-soo-saarka xad-dhaafka ah ay inta badan ku dhacdo cudurrada caabuqa ee daba-dheeraada, Dr. Kishimoto wuxuu sharxay in xasilinta IL-6 ay si xooggan ugu tiirsan tahay rasuulkeeda RNA. Si loo samata bixiyo bukaanada la ildaran CAR-T dabaylaha cytokine ee unugyadu keento, qaar badan oo ka mid ah xirfadlayaasha caafimaadka ayaa hadda isticmaali doona tocilizumab si ay u yareeyaan waxyeelada daawayntan. Marka la eego tusaalahan, Dr. Kishimoto iyo kooxdiisu waxay qiyaaseen in tocilizumab ay sidoo kale waxtar u yeelan karto caawinta bukaannada aadka u buka ee COVID-19 la dagaalanka duufaannada cytokine. Dhowr tijaabo oo caafimaad oo waaweyn ayaa caddeeyey inay hoos u dhigi karto suurtogalnimada u baahan hawo-qaadasho ama khatarta dhimashada. Sababtan awgeed, Maamulka Cunnada iyo Dawooyinka ee Mareykanka iyo Ururka Caafimaadka Adduunka labaduba waxay soo saareen Oggolaanshaha Isticmaalka Degdegga ah ee tocilizumab ee daaweynta bukaannada COVID-19. Muxaadaradan, Dr. Kishimoto wuxuu inagu siiyay dulmar guud oo ku saabsan cilmi baadhista IL-6 ee uu hogaaminayay kooxdiisu 50kii sano ee la soo dhaafay. Waxay ahayd safar iyaga ka soo qaaday cilmi-baaris aasaasi ah oo u gudbay horumarinta daroogada iyo codsiga bukaan-socodka.

Saddexdan muxaadaro ee abaal marinta Tang Prize ee Sayniska Biopharmaceutical Science 2020 waxaa lagu daah-furi doonaa kanaalka Tang Prize YouTube laga bilaabo 4 galabnimo ilaa 7 galabnimo (GMT+8) Noofambar 27.

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Linda S. Hohnholz

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