Ukwelashwa Okusha Kuveza Izimpendulo Eziphawulekayo Ezivivinyweni Zokuqala
Eyaziwa ngokuthi i-adopting cell transfer (ACT), lokhu kuyindlela entsha yokwelashwa okubandakanya ubunjiniyela amangqamuzana omzimba omzimba ukuze abone futhi ahlasele amaseli abo omzimba. Nakuba lolu hlobo lwamayeza okwamanje luhlolwa futhi luvinjelwe ezinyangeni ezincane zokwelashwa ezincane kuze kube manje, liye labonisa izimpendulo ezithakazelisayo ezigulini zomdlavuza ophakeme.
Indlela Esebenza ngayo
Ama-T-cell, uhlobo lwamasosha omzimba, akhona nama-receptors ebusweni bawo, okuthiwa yi-T-cell receptors, noma ama-TCR. Ngokuvamile lezi TCR zibopha ama-antigens ukuze zikhishwe impendulo yomzimba. Emzamweni wokusebenzisa i-T-cell for therapy, i-T-seli iqoqwa kusuka egazini likagciwane. Khona-ke, esibhedlela, ama-T-amangqamuzana aguqulwa ukuze akhiqize ama-receptors akhethekile ebusweni bawo okuthiwa i-chimeric antigen receptors, noma ama-CAR, akwazi ukubopha amaprotheni angaphansi kwamangqamuzana athile omdlavuza.
Ama-CAR T-cell ahlanganisiwe avunwa ebhodini futhi avunyelwe ukwandisa izinombolo zawo kuze kube yizigidigidi zazo. Ngokulandela ukuguqulwa nokuvunwa, lawa maseli-T, ahlinzeka ngama-CAR angakwazi ukubona nokubulala amakhemikhali athile omdlavuza, abuye aphinde abuyele esibhedlela.
Lezi CAR ziyi-protein ezenza ama-T-cell aqaphele iphrotheni ethile, noma i-antigen, kuma-cell tumor.
Ama-CAR T-cells akhiwe asekhulile ebhodini futhi avunyelwe ukwandisa izinombolo zabo kuze kube yizigidigidi zazo. Kuze kube manje, ukuthi ukusebenza kahle kangakanani kuncike ekutheni kuncike ekutheni bakwazi ukukhula futhi bahlale bekhuthele esigulini ngemuva kokungena ngaphakathi.
Umqondo wokusebenzisa amangqamuzana abukhoma ukwelapha umdlavuza empeleni awuntsha.
Izifundo ezifundwe emiphumeleni yezokwelapha ezifanayo esikhathini esidlule zaholela ekuzuzeni ulwazi lokuthi ama-T-cell asebenza kanjani , okwenza kube nokuthola okuningi. Abaphenyi abasebenza kule nsimu baqaphele ukuthi kusadingeka bafunde okuningi nge-CAR T-cell therapy. Kodwa imiphumela yokuqala ekuhlolweni okufana nalezi zenzele ithemba elincane.
Uphumelela Kakhulu Kangaka
Abanye baye bafanisa loluhlobo lwezokwelapha ekuhlanganisweni kwezinhlobo ezimbili zokwelashwa ezihlukene: amasosha omzimba ahlosiwe, njenge-rituximab, enezimpawu zabo; kanye ne-cancer-cell-kill-agents ephethe amandla e- cytotoxicity - konke lokhu okukhona ngokukhona kwesikhathi eside kwezinto eziphilayo ze-cytotoxic T-cells, ngokwethemba ukuthi zihlale zisakazwa, ukuqapha ukuphindaphindiwe.
Ucwaningo luyinto entsha kakhulu, ngakho-ke ochwepheshe banxusa ukuqapha, kodwa ukuhlolwa kwemitholampilo sekuqalile ukusebenzisa izindlela zokwelashwa zase-CAR T-cell kulezi zifo ezilandelayo:
- I-melanoma ephakeme
- I-Advanced acute lymphoblastic leukemia (YONKE)
- Ukusakaza i-B-cell lymphoma enkulu
I-FDA ikhethe ukwelashwa kwe-CAR T-cell ukwelashwa okuphumelelayo kubo bonke. Iphinde ihlolwe ngokuphindaphindiwe nokuphikisana non-Hodgkin lymphoma, i-myeloma, ne- chronic lymphocytic leukemia (CLL) , kanye neziguli ezine-non-Hodgkin lymphoma ne-myeloma.
Abaphenyi bethemba i-CAR T-cell therapy izokwenziwa ngelinye ilanga libe yindlela yokwelashwa ejwayelekile yamanye amabizo e-B-cell njenge-ALL AND chronic lymphocytic leukemia. Abacwaningi abasebenza nama-CAR-T-cell baye baqaphela loluhlobo lwezokwelapha njenge "bhuloho" ekutheni ukuguqulwa komnyoba kuWONKE iziguli eziyeka ukuphendula ekhemotherapy.
Esinye isilingo sibheke ukusetshenziswa kwama-CAR T-cell ku-15 iziguli ezikhulile, futhi iningi lawo lalinomzimba omkhulu we-B-cell lymphoma. Nakuba kungangabazeki ukuthi isilingo esincane, ithemba livela eqinisweni lokuthi iningi lalezi ziguli eziphathwe ngama-CAR T-cells zinezimpendulo eziphelele noma eziyingxenye.
Kukhona nethemba lokuthi i-CAR T-cell therapy ingasetshenziswa ukuvimbela ukubuyela emuva. Ezinye iziphumo ezenza kube nethemba zihlanganisa ukukhuliswa kwamaseli wokwelapha ngemva kokukhipha , okungaphezu kwezigidi eziyi-1000 kwabanye abantu; kanye nokuba khona kwama-CAR T-cell ohlelweni oluyisisekelo senzwa, "indawo engcwele" lapho amangqamuzana omdlavuza owodwa ophunywe khona ngamakhemikhali noma imisebe ingase ifihlwe. Kulezi ziguli ezimbili ezivivinyweni zokutholwa kwabazali be-NCI, isibonelo, ukwelashwa kwe-CAR T-cell kwaqeda umdlavuza owasakazekele ohlelweni lwezinzwa zomphakathi.
Okuqhamuka uma udla imishanguzo
Uma inani elikhulu lama-T-cell alungiswayo aphinde aphinde ahanjiswe esibhedlela, lawa maseli-T akhipha ama-cytokines ngemali enkulu. Lokhu kungabangela i-cytokine-release release syndrome, ekhonjiswe ngamapayipi aphezulu ngokuyingozi futhi iholele ekucindezeni kwegazi. Ama-Cytokines ayimpawu zamakhemikhali, futhi i-cytokine-release release isifo esivamile kwiziguli eziphathwe ngama-CAR T-cell.
Iziguli ezinomthelela omkhulu kakhulu womdlavuza ngaphambi kokuthola ama-CAR T-cells zibonakala zinamathuba amaningi okuba nezimo ezinzima ze-cytokine-release release. Abacwaningi baqaphele ukuthi naphezu kwempumelelo, ucwaningo olwengeziwe luyadingeka ngaphambi kokuba i-CAR T-cell therapy ingabi yindlela yokujwayela, ngeziguli ezine-NONKE isibonelo. Izifundo ezineziguli eziningi kanye nezinkathi zokulandelela ezinde zibizelwe futhi zilandelwa.
On the Horizon
Ngokusukela empumelelweni kuze kube manje, amaqembu amasha okucwaninga ezweni lonke ahlolisisa ekuthuthukiseni amangqamuzana e-T ayenziwe ngamanye amagciwane, kuhlanganise nezicubu eziqinile ezifana ne-pancreatic and cancers.
> Imithombo:
> Ukwelashwa kwe-CAR T-Cell: Ama-Immune Cell 'Ama-Immune Cell to Treat Their Cancers. http://www.cancer.gov/cancertopics/research-updates/2013/CAR-T-Amadivayisi.
> Barrett DM, Singh N, Porter DL, Grupp SA, Juni CH. I-Chimeric Antigen Receptor Therapy for Cancer. Annu Rev Med . 2014; 65: 333-347.
> I-Chimeric Antigen Receptor T-Cell. http://www.lymphomation.org/programing-t-cells.htm.