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Ochwepheshe ku-Cincinnati Children's report, kumagundane, ukuthi ukwelashwa kwe-antibody kungathuthukisa ukusinda uma uhlobo oluthile 'lwesiphepho se-cytokine' luhlasela.

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Kungakhathaliseki ukuthi yizingane ezibhekana nezifo ezingavamile zokuzivikela komzimba noma iziguli ezinomdlavuza ezifuna izindlela zokwelapha ezintsha ezithembisayo, abantu abaningi bafunda ngohlobo oluvame ukubulala amasosha omzimba olubizwa ngokuthi “isiphepho se-cytokine.”              

Odokotela nososayensi abazi ngeziphepho ze-cytokine isikhathi eside nabo bayazi ukuthi izici eziningi zingabandakanyeka ekuzibangeleni, futhi ukwelashwa okumbalwa kuphela okungazibambezela. Manje, ithimba elivela ku-Cincinnati Children's libika impumelelo yangaphambi kwesikhathi ekulawuleni ezinye izivunguvungu ze-cytokine ngokuphazamisa amasignali aphuma kumaseli e-T acushiwe amasosha ethu omzimba. 

Okutholiwe okuningiliziwe kwashicilelwa Jan. 21, 2022, ku-Science Immunology. Lolu cwaningo lunababhali abathathu abahamba phambili: uMargaret McDaniel, u-Aakanksha Jain, no-Amanpreet Singh Chawla, PhD, bonke ababekade beneCincinnati Children's. Umbhali ohambelana naye kwakungu-Chandrashekhar Pasare, DVM, PhD, Professor, Division of Immunobiology and Co-Director of Centre for Inflammation and Tolerance at Cincinnati Children's.

"Lokhu kutholakala kubalulekile ngoba sikhombisile, kumagundane, ukuthi izindlela zokuvuvukala zesistimu ezihilelekile kulolu hlobo lwesiphepho se-T cell-driven cytokine zingancishiswa," kusho uPasare. “Kuzodingeka umsebenzi omningi ukuze kuqinisekiswe ukuthi indlela esiyisebenzisa kumagundane ingase iphephe futhi isebenze kahle kubantu. Kodwa manje sinenhloso ecacile okufanele siyilandele.”

Siyini isiphepho se-cytokine?

Ama-Cytokines angamaprotheni amancane afihliwe cishe yizo zonke izinhlobo zamaseli. Inqwaba yama-cytokine aziwayo enza uxhaxha lwemisebenzi ebalulekile, evamile. Emasosheni omzimba, ama-cytokines asiza ukuqondisa ama-T-cell namanye amaseli omzimba ukuze ahlasele futhi asuse amagciwane ahlaselayo namagciwane kanye nokulwa nomdlavuza.

Kodwa ngezinye izikhathi, “isiphepho” se-cytokine siphumela ekubeni nama-T cell amaningi kakhulu empini. Umphumela ungaba ukuvuvukala okudlulele okungabangela umonakalo omkhulu, ngisho nokubulala izicubu ezinempilo.

Ucwaningo olusha lunikeza ukukhanya ngenqubo yokusayina ezingeni lamangqamuzana. Ithimba libika ukuthi okungenani izindlela ezimbili ezizimele zikhona ezibangela ukuvuvukala emzimbeni. Nakuba kunendlela eyaziwa futhi esungulwe yokuvuvukala yokusabela kubahlaseli bangaphandle, lo msebenzi uchaza indlela engaqondakali eqhuba umsebenzi wokuzivikela omzimba “oyinyumba” noma ongahlobene nezifo.

Izindaba ezinethemba lokunakekelwa komdlavuza

Okubili kwentuthuko yokunakekelwa komdlavuza ejabulisa kakhulu eminyakeni yamuva nje kube ukuthuthukiswa kwama-checkpoint inhibitors kanye ne-chimeric antigen receptor T cell therapy (CAR-T). Lezi zindlela zokwelapha zisiza ama-T cell ukuthi abone futhi abhubhise amangqamuzana omdlavuza ngaphambili abevika izivikelo ezingokwemvelo zomzimba.

Imithi eminingana esekelwe kubuchwepheshe be-CAR-T ivunyelwe ukwelapha amalungelo obunikazi alwa nokusabalalisa i-B-cell lymphoma (DLBCL), i-follicular lymphoma, i-mantle cell lymphoma, i-myeloma eminingi, kanye ne-B-cell acute lymphoblastic leukemia (YONKE). Okwamanje. inqwaba ye-checkpoint inhibitors isiza abantu abanomdlavuza wamaphaphu, umdlavuza webele kanye nezinye izifo eziningi ezimbi. Lezi zindlela zokwelapha zihlanganisa i-atezolizumab (Tecentriq), avelumab (Bavencio), cemiplimab (Libtayo), dostarlimab (Jemperli), durvalumab (Imfinzi), ipilimumab (Yervoy), nivolumab (Opdivo), ne-pembrolizumab (Keytruda).

Kodwa-ke, kwezinye iziguli, lezi zindlela zokwelapha zingavumela izinkumbi zama-T-cell ukuthi ahlasele izicubu ezinempilo kanye nomdlavuza. Ochungechungeni lwegundane nokuhlolwa kwaselabhorethri, ithimba locwaningo e-Cincinnati Children's libika ukuthi lilandelela phansi umthombo wokuvuvukala okubangelwa yilokhu kungaziphathi kahle kwe-T cell futhi libonisa indlela yokukunqanda.

"Sihlonze i-node ebalulekile yokubonisa esetshenziswa ama-memory memory T cell (TEM) ukuhlanganisa uhlelo olubanzi lwe-proinflammatory kusistimu yokuzivikela engaphakathi," kusho uPasare. "Sithole ukuthi ubuthi be-cytokine kanye ne-autoimmune pathology bungahlengwa ngokuphelele kumamodeli amaningi okuvuvukala okuqhutshwa yi-T cell ngokuphazamisa lezi zimpawu ngokuhlelwa kwezakhi zofuzo noma ngamakhompiyutha amancane."

Ngaphandle kokwelashwa, amaphesenti angu-100 amagundane akhangwe ukuba abe nesiphepho se-cytokine njengalawo aqalwa ukwelashwa kwe-CAR-T afa zingakapheli izinsuku ezinhlanu. Kodwa amaphesenti angu-80 amagundane aphathwe ngamasosha omzimba ukuze avimbe amasignali avela kumaseli T acushiwe asinda okungenani izinsuku eziyisikhombisa.

Ukutholwa akusebenzi ku-COVID-19

Abantu abaningi abanezifo ezinzima ezivela ku-SARS-CoV-2 virus nabo bake babhekana neziphepho ze-cytokine. Nokho, kunomehluko obalulekile phakathi kokuvuvukala kwesistimu okubangelwa ukutheleleka ngegciwane kanye nalolu hlobo “oluyinyumba” lokuvuvukala okubangelwa ama-T cell acushiwe.

"Sithole iqoqo lezakhi zofuzo ezikhishwa ngokukhethekile ngamaseli e-TEM angabandakanyeki ekuphenduleni ukutheleleka ngegciwane noma amagciwane," kusho uPasare. "Lokhu kusho ukuguquguquka okuhlukile kwalezi zindlela ezimbili zokwenza kusebenze ngaphakathi."

Izinyathelo ezilandelayo

Ngokombono, ukwelashwa kwe-antibody okufana nalokhu okusetshenziswe ezifundweni zegundane kunganikezwa iziguli ezinomdlavuza ngaphambi kokuba zithole ukwelashwa kwe-CAR-T. Kodwa ucwaningo olwengeziwe luyadingeka ukuze kutholwe ukuthi indlela enjalo iphephe ngokwanele yini ukuthi ihlolwe ezivivinyweni zomtholampilo zabantu.

Ngaphezu kokwenza uhlobo oluthembisayo lokunakekelwa komdlavuza lufinyeleleke kubantu abaningi, ukulawula le ndlela yokuvuvukala oyinyumba kungase kube usizo ezinganeni ezizalwe zinesinye sezifo ezintathu ezingavamile kakhulu zokuzivikela komzimba ezivikela ukuzivikela ezifweni, okuhlanganisa i-IPEX syndrome, ebangelwa ukuguqulwa kofuzo lwe-FOXP3; Isifo se-CHAI, esibangelwa ukungasebenzi kahle kofuzo lwe-CTLA-4; kanye nesifo se-LATIAE, esibangelwa ukuguquka kofuzo lwe-LRBA. 

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