Indlela eNtsha yokuThintela iziPhumo eziMandundu zoNyango loKhuseleko lweCancer

Ibhalwe ngu umhleli

Iingcaphephe kwingxelo yaBantwana yaseCincinnati, kwiimpuku, ukuba unyango lwe-antibody lunokuphucula ukuphila xa uhlobo oluthile lwe 'cytokine storm' luhlasela.

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Nokuba ngabantwana abajongana nezifo ezinqabileyo ze-autoimmune okanye abaguli abanomhlaza abafuna unyango olutsha oluthembisayo, abantu abaninzi bafunda ngohlobo oluhlala lubulala kakhulu lwamajoni omzimba olubizwa ngokuba “sisivunguvungu secytokine.”              

Oogqirha kunye noosonzululwazi abazaziyo malunga nezaqhwithi ze-cytokine ixesha elide bayazi ukuba zininzi izinto ezinokubandakanyeka ekuzibangeleni, kwaye lunyango olumbalwa kuphela olunokuthothisa. Ngoku, iqela elivela kwiCincinnati yaBantwana linika ingxelo yempumelelo yakwinqanaba lokuqala ekudambiseni izaqhwithi ze-cytokine ngokuphazamisa imiqondiso evela kwiiseli ze-T ezisebenzayo kumajoni ethu omzimba. 

Iziphumo ezineenkcukacha zipapashwe ngoJanuwari 21, 2022, kwi-Science Immunology. Uphononongo lunababhali abathathu abahamba phambili: uMargaret McDaniel, u-Aakanksha Jain, kunye no-Amanpreet Singh Chawla, PhD, bonke ababekade benabantwana baseCincinnati. Umbhali ohambelanayo ophezulu ngu-Chandrashekhar Pasare, i-DVM, i-PhD, uProfesa, iCandelo le-Immunobiology kunye no-Co-Director of Centre for Inflammation and Tolerance kwi-Cincinnati Children's Children.

"Oku kufunyaniswa kubalulekile kuba sibonise, kwiigundane, ukuba iindlela zokuvuvukala zenkqubo ezibandakanyekayo kulolu hlobo lwe-T cell-driven cytokine storm zinokuncitshiswa," kusho uPasare. “Kuza kufuneka umsebenzi omninzi ukuqinisekisa ukuba indlela ebesiyisebenzisa kwiimpuku inokukhuseleka kwaye isebenze ebantwini. Kodwa ngoku sinenjongo ecacileyo ekufuneka siyilandele. ”

Yintoni isaqhwithi secytokine?

IiCytokines ziiproteni ezincinci ezifihliweyo phantse kulo lonke uhlobo lweeseli. Uninzi lweecytokines ezaziwayo zenza uluhlu lwemisebenzi ebalulekileyo, eqhelekileyo. Kwi-immune system, ii-cytokines zinceda ukukhokela iiseli ze-T kunye nezinye iiseli zokuzivikela ukuba zihlasele kwaye zisuse iintsholongwane ezihlaselayo kunye neebhaktheriya kunye nokulwa nomhlaza.

Kodwa maxa wambi, “isaqhwithi” secytokine siphumela ekubeni neeT seli ezininzi edabini. Isiphumo sinokuba kukudumba okugqithisileyo okunokubangela ukonakala okugqithisileyo, kwanokubulala kwizicubu eziphilileyo.

Uphando olutsha lukhanyisela inkqubo yokubonisa kwinqanaba le-molecular. Iqela libika ukuba ubuncinane iindlela ezimbini ezizimeleyo zikhona ezibangela ukuvuvukala emzimbeni. Nangona kukho indlela eyaziwayo kunye nesekiweyo yokukrala yokusabela kubahlaseli bangaphandle, lo msebenzi uchaza indlela engaqondakaliyo eqhuba "inyumba" okanye i-non-infection-related immune immune.

Iindaba ezinethemba lokhathalelo lomhlaza

Emibini yezona zinto zinomdla kakhulu zophuhliso lomhlaza kwiminyaka yakutshanje ibe luphuhliso lwe-checkpoint inhibitors kunye ne-chimeric antigen receptor T cell therapy (CAR-T). Ezi ntlobo zonyango zinceda iiseli ze-T zibhaqe kwaye zitshabalalise iiseli zomhlaza ebezifudula ziluphepha ukhuselo lwendalo lomzimba.

Amachiza amaninzi asekelwe kubuchwephesha be-CAR-T avunyiweyo ukunyanga amalungelo awodwa abenzi bokubi alwa ne-B-cell lymphoma (DLBCL), i-follicular lymphoma, i-mantle cell lymphoma, i-myeloma emininzi, kunye ne-B-cell acute lymphoblastic leukemia (YONKE). Okwangoku. inani le-checkpoint inhibitors linceda abantu abanomhlaza wemiphunga, umhlaza wamabele kunye nezinye izifo ezininzi. Olu nyango lubandakanya i-atezolizumab (Tecentriq), avelumab (Bavencio), cemiplimab (Libtayo), dostarlimab (Jemperli), durvalumab (Imfinzi), ipilimumab (Yervoy), nivolumab (Opdivo), kunye ne-pembrolizumab (Keytruda).

Nangona kunjalo, kwezinye izigulana, olu nyango lunokuvumela iiseli ze-T ezikhohlakeleyo ukuba zihlasele izicubu ezinempilo kunye nomhlaza. Kuluhlu lwemouse kunye novavanyo lwebhubhoratri, iqela lophando kwiCincinnati Children's report lilandelela phantsi umthombo wokudumba okubangelwa yile T cell yokuziphatha kakubi kwaye ibonisa indlela yokuthintela.

"Sichonge i-node ebalulekileyo yokubonakalisa i-node esetyenziswa yi-memory memory T cells (TEM) ukudibanisa inkqubo ebanzi yokuvuvukala kwi-immune system," kusho uPasare. "Sifumene ukuba i-cytokine toxicity kunye ne-autoimmune pathology inokuhlangulwa ngokupheleleyo kwiimodeli ezininzi zokudumba okuqhutywa yi-T cell ngokuphazamisa le miqondiso mhlawumbi ngokuhlelwa kofuzo okanye ngeekhompawundi ezincinci zemolekyuli."

Ngaphandle konyango, i-100 lepesenti yeempuku eziye zafumana isaqhwithi se-cytokine ezifana nezo ziqaliswe lunyango lwe-CAR-T zafa phakathi kweentsuku ezintlanu. Kodwa i-80 pesenti yeempuku ezinyangwa ngamajoni omzimba ukubhloka iimpawu eziphuma kwiiseli T ezisebenzayo zasinda ubuncinane iintsuku ezisixhenxe.

Ukufunyaniswa akusebenzi kwi-COVID-19

Abantu abaninzi abanosulelo oluqatha oluvela kwintsholongwane ye-SARS-CoV-2 nabo baye bafumana izaqhwithi ze-cytokine. Nangona kunjalo, kukho iiyantlukwano ezibalulekileyo phakathi kokudumba kwenkqubo okubangelwa lusulelo lwentsholongwane kunye nolu hlobo "lunyumba" lokudumba olwenziwa ziiseli ze-T ezisebenzayo.

"Sichonge iqoqo leejeni eziye zenziwe ngokukodwa ngeeseli ze-TEM ezingabandakanyekanga kwimpendulo yosulelo lwentsholongwane okanye ibhaktheriya," kusho uPasare. "Oku kubonisa inguqu eyahlukileyo kwezi ndlela zimbini zokuvula ngaphakathi."

Amanyathelo alandelayo

Ngokwethiyori, unyango lwe-antibody olufana nolo lusetyenziswe kwizifundo zempuku lunokunikwa izigulana ezinomhlaza phambi kokuba zifumane unyango lwe-CAR-T. Kodwa uphando oluninzi luyafuneka ukufumanisa ukuba indlela enjalo ikhuselekile ngokwaneleyo ukuvavanya kulingo lwezonyango lomntu.

Ngaphandle kokwenza uhlobo oluthembisayo lokhathalelo lomhlaza lufikeleleke kubantu abaninzi, ukulawula le ndlela yokudumba eyinyumba inokuba luncedo kubantwana abazelwe benesinye sezifo ezithathu ezinqabileyo kakhulu ze-autoimmune, kubandakanywa i-IPEX syndrome, ebangelwa kukuguqulwa kwemfuza ye-FOXP3; Isifo se-CHAI, esibangelwa kukungasebenzi kakuhle kwe-CTLA-4 gene; kunye nesifo se-LATIAE, esibangelwa kukuguqulwa kwemfuza ye-LRBA. 

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Umhleli oyintloko we-eTurboNew nguLinda Hohnholz. Uzinze kwi-eTN HQ e-Honolulu, eHawaii.

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