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Kafukufuku wa Cancer ndi COVID: Udindo wa Cytokines

Written by Linda S. Hohnholz

Kutsatira mawu olimbikitsa otsegulira, "Future Perspective of Cancer Immunotherapy," yoperekedwa ndi Mphotho ya Nobel komanso Wopambana Mphotho ya Tang Prof. Tasuku Honjo pa 14th Asia Pacific Federation of Pharmacologist Conference (APFP) pa Novembara 26, 2020 Tang Prize Laureate Lecture for Biopharmaceutical Sayansi, yokonzedwa ndi Tang Prize Foundation ndi The Pharmacological Society ku Taiwan, idachitika pa 14th APFP nthawi ya 1:30 pm (GMT+8) pa Novembara 27.

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Mothandizidwa ndi Dr. Wen-Chang Chang, wapampando wa oyang'anira a Taipei Medical University, ndi Dr. Yun Yen, pulofesa wapampando ku Taipei Medical University, gawo lapaderali linali ndi nkhani zokambidwa ndi opambana atatu pa Mphotho ya 2020 Tang mu Biopharmaceutical Science. , Dr. Charles Dinarello, Marc Feldmann, ndi Tadamitsu Kishimoto, akupereka chidziwitso chofunikira pa ntchito ya ma cytokines pa kutupa ndi matenda a COVID-19 komanso chithandizo chotheka.

Nkhani yoyamba ya Dr. Dinarello, yotchedwa "Interleukin-1: The Prime Mediator of Systemic and Local Inflammation," inayamba ndi kuyeretsa kwake leukocytic pryogen kuchokera ku maselo oyera a magazi aumunthu mu 1971. Kenako zinamutengera zaka zisanu ndi chimodzi kuti azindikire malungo awiri- kupanga mamolekyu, omwe pambuyo pake adatchedwa IL-1αndi IL-1β. Mu 1977, zotsatira za kafukufuku zinasindikizidwa mu Proceedings of the National Academy of Sciences, ndipo kwa Dr. Dinarello, "imeneyi inali sitepe yofunika kwambiri m'mbiri ya cytokine biology," chifukwa anthu ambiri a sayansi ya zamoyo analimbikitsidwa kuti azitsatira. kuphunzira momwe chitetezo cha mthupi chimakhudzira thupi la munthu. Chifukwa cha zimenezi, biology ya cytokine inakula mofulumira. Ananenanso za momwe pambuyo poyesera koyambirira kwa anthu, "mbiri ya ma cytokines omwe amagwiritsidwa ntchito ngati chithandizo adasinthiratu kwambiri," ndipo cholinga chake chidasinthidwa kukhala "kuletsa ma cytokines, monga IL-1, monga TNF, monga IL- 6.” Pofuna kuthandiza omvera kuti amvetse zovuta zomwe zimagwirizanitsidwa ndi mamolekyu okhudzana ndi kutupa a banja la IL-1, Dr. Dinarello adalongosola za kusintha kwa chizindikiro cha mamembala a banja la IL-1, makhalidwe awo ochiritsira komanso odana ndi kutupa, ndi zizindikiro za matenda osiyanasiyana otupa, kuti achepetse njira yoti omvera amvetse bwino theka lachiwiri la nkhani yomwe idakhudza "kugwiritsa ntchito kwachipatala kwa blockade ya Il-1." Kuchulukitsa kwa IL-1, monga momwe Dr. Dinarello adanenera, ndizomwe zimayambitsa matenda ambiri. IL-1Ra, kumbali ina, ikhoza kuletsa Il-1αandβ, ndikuletsa chizindikiro cha IL-1R. Anakinra, munthu wophatikizanso IL-1Ra wapangidwa. Amagwiritsidwa ntchito pochiza nyamakazi ya nyamakazi komanso amatha kupewa zovuta za glycemic mumtundu wa 2 shuga. Komanso, canakinumab, anti-IL-1βmonoclonal antibody yopangidwa bwino ndi Novartis, yavomerezedwa ndi matenda osiyanasiyana, kuyambira matenda osowa cholowa, matenda a rheumatic, autoimmune ndi kutupa, ku matenda a mtima. Nkhani yosangalatsa kwambiri yokhudza canakinumab ndi kuyesa kwachipatala, CANTOS, komwe kunatsimikizira mosayembekezereka kuti canakinumab ili ndi gawo lofunikira pochiza khansa. Choncho, Dr. Dinarello amakhulupirira kuti kutsekereza IL-1 kungayambitse mbandakucha wa chithandizo chatsopano cha khansa.

Wokamba nkhani wachiŵiri, Dr. Feldmann, anafotokoza maganizo ake ponena za “Kumasulira Molecular Insights in Autoimmunity to Effective Therapy.” Kutsindika kwa theka loyamba la nkhani yake kunali momwe adadziwira kuti anti-TNF ikhoza kukhala yothandiza pochiza nyamakazi ya nyamakazi. Kuwongolera mlingo waukulu kapena wochepa wa mankhwalawa ukhoza kulepheretsa TNF komanso kuchepetsa mofulumira kupanga oyimira ena otupa. M'mayesero awo oyambirira, Dr. Feldmann ndi gulu lake adawonetsa kuti pafupifupi 50% ya anthu omwe ali ndi nyamakazi ya nyamakazi adayankha kusakaniza mankhwala pogwiritsa ntchito anti-TNF ndi methotrexate ya khansa ya khansa. Izi zinamupangitsa kukhulupirira kuti “pali patali kwambiri kuti wodwala aliyense achire.” Mkati mwa theka lachiŵiri la nkhaniyo, Dr. Feldmann anatiuza kuti “TNF ndi yosinkhasinkha yachilendo kwambiri, chifukwa ili ndi zolinga ziwiri zosiyana: TNF receptor-1 (TNFR1), yomwe imayambitsa kutupa, ndi TNF receptor 2, yomwe imachita kwambiri. mosiyana. Chifukwa chake mukaletsa TNF yonse, mumatsekereza zolandilira. Mumaletsa kutupa, koma mumalepheretsanso thupi kuti lichepetse kutupako.” Choncho, iye ndi anzake "akupanga zida" ndipo adatseka kale TNFR1 popanda kusintha ntchito ya maselo a T olamulira. Kuonjezera apo, Dr. Feldmann adanena za kuthekera kwa anti-TNF pofuna kuthana ndi zosowa zambiri zachipatala zomwe sizikugwirizana nazo, monga kuchiza fibrosis m'manja mwa kubaya anti-TNF m'manja. Komabe, adawonetsa zovuta ziwiri zodziwikiratu za anti-TNF yomwe adayamba kupanga: inali yotsika mtengo komanso "inali mankhwala obaya." Motero, kupanga “mankhwala otchipa operekedwa pakamwa” kungabweretse phindu lalikulu kwa anthu. M’nkhani yonseyi, Dr. Feldmann anapitirizabe kulera anthu ambiri amene anali nawo kapena akugwira nawo ntchito zosiyanasiyana ndi zoyesayesa zosiyanasiyana, pamene anayesera kumveketsa uthenga wakuti zimene anaphunzira m’zokumana nazozi zinali “momwe angagwiritsire ntchito bwino ndi ena” kuti awonetsetse kuti kafukufuku wawo akupita patsogolo. Chakhala chizindikiro cha ntchito yake kupeza “anthu aluso oti agwire nawo ntchito,” komanso, “pamodzi nawo,” kuti akwaniritse zambiri “kuposa tokha.”

Pokamba nkhani yachitatu pamutu wakuti "Interleukin-6: Kuchokera ku Arthritis kupita ku CAR-T ndi COVID-19," Dr. Kishimoto adakokera chidwi cha omvera momwe IL-6 idatulukira, chifukwa chiyani IL-6 ndi molekyulu ya pleiotropic, ndipo chifukwa chiyani IL-6 "imayang'anira kupanga ma antibodies komanso kuyambitsa kutupa." Anawunikiranso za zotsatira za IL-6 pa matenda a autoimmune komanso momwe IL-6 ingayambitsire mkuntho wa cytokine. Kumayambiriro kwa nkhani yake, Dr. Kistimoto adanena momveka bwino kuti kuchulukitsa kwa IL-6 kwapeza kuti kumakhudzana ndi matenda ambiri, monga mtima wa myxoma, matenda a Castleman, nyamakazi ya nyamakazi, ndi kuyambika kwa matenda a ana a idiopathic (JIA). Pofuna kuthana ndi mayankho otupa omwe adayambitsa IL-6 overproduction, Dr. Kishimoto ndi gulu lake anayesa kuchiza odwala poletsa zizindikiro za IL-6. Pambuyo pake, tocilizumab, anti-IL-6 recombinant humanized anti-IL-100 receptor monoclonal antibody, idapangidwa bwino ndipo yavomerezedwa kuti igwiritsidwe ntchito m'maiko opitilira 6 pochiza nyamakazi ya nyamakazi ndi JIA. Pankhani ya momwe kupanga IL-6 kumayendetsedwa komanso chifukwa chake kuchulukitsa kwa IL-6 nthawi zambiri kumachitika m'matenda otupa osatha, Dr. Kishimoto adalongosola kuti kukhazikika kwa IL-19 kumadalira kwambiri mthenga wake RNA. Pofuna kupulumutsa odwala omwe akuvutika ndi mphepo yamkuntho ya CAR-T cell-induced cytokine, ambiri ogwira ntchito zachipatala tsopano agwiritsa ntchito tocilizumab kuti athetse zotsatira za mankhwalawa. Potengera chitsanzo ichi, Dr. Kishimoto ndi gulu lake anaganiza kuti tocilizumab itha kuthandizanso odwala omwe ali ndi COVID-19 omwe akudwala kwambiri kuthana ndi mkuntho wa cytokine. Mayesero akuluakulu angapo azachipatala adatsimikizira kuti amatha kuchepetsa mwayi wofuna mpweya wabwino kapena chiwopsezo cha imfa. Pazifukwa izi, US Food and Drug Administration ndi World Health Organisation onse apereka Chilolezo Chogwiritsa Ntchito Mwadzidzidzi kwa tocilizumab pochiza odwala a COVID-6. Pankhani iyi, Dr. Kishimoto adatipatsa chithunzithunzi chokwanira cha kafukufuku wa IL-50 yemwe adatsogolera gulu lake pochita zaka XNUMX zapitazi. Unali ulendo womwe unawatengera kuchokera ku kafukufuku woyambira kupita ku chitukuko cha mankhwala ndi kugwiritsa ntchito kuchipatala.

Nkhani zitatu izi zoperekedwa ndi omwe adalandira Mphotho ya 2020 Tang mu Biopharmaceutical Science adzawonetsedwa panjira ya Tang Prize YouTube kuyambira 4pm mpaka 7pm (GMT + 8) pa Novembara 27.

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Linda S. Hohnholz

Linda Hohnholz wakhala mkonzi wamkulu wa eTurboNews kwa zaka zambiri.
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