Ukutolikwa okubanzi koNyango lweeT-Cell zeCAR

I-CAR-T (i-Chimeric Antigen Receptor T-Cell), emele ii-chimeric antigen receptor T-cells, yinkqubo apho ii-T cells zomntu zenziwe ngokwezakhi zofuzo ngaphandle komzimba ukuze zitshintshwe, zinike amandla okubona nokubulala iiseli zomhlaza ngokufanelekileyo ngaphambi kokuba ziphinde zifakwe emzimbeni wesigulana, ngaloo ndlela zifezekisa injongo yokunyanga iithumba ezinobungozi.
Enyanisweni, unyango lwe-CAR-T alusetyenziselwa kuphela ukunyanga umhlaza kodwa lukwanamandla amakhulu kwicandelo lezifo ezizikhuselayo emzimbeni, usulelo olungapheliyo, isifo sentliziyo, kunye nezifo ezinxulumene nobudala.
Ii-T cells, ezaziwa ngokuba zii-T lymphocytes, zezona zinto ziphambili kwii-lymphocytes kwaye zinoxanduva olukhulu lokuphendula kwi-immune system kunye nokukhusela izifo. Zinemisebenzi efana nokubulala ngokuthe ngqo ii-immune cells, ukunceda nokuthintela ii-B cells ukuba zivelise ii-antibodies, ukuphendula kwii-antigens ezithile kunye nee-mitogens, kunye nokuvelisa ii-cytokines.
Kakade ke, inkqubo yomzimba yokuzikhusela ayipheleli kwiiseli ze-T kuphela; ikwaquka iiseli ze-B, ii-neutrophils, iiseli ze-K, iiseli ze-NK, nezinye. Zidlala indima ekususeni imveliso ye-metabolism emzimbeni, ukuqaphela nokuvelisa ii-antibodies, kunye nokuchonga nokubulala iintsholongwane zangaphandle kunye neeseli zomhlaza.
Ekubeni ii-T cells sele zinomsebenzi wokubona nokubulala iiseli zomhlaza, kutheni kuyimfuneko ukongeza i-CAR kwiiseli ze-T ngokwenziwa ukuze kudalwe iiseli ze-CAR-T zokubulala iiseli zomhlaza? Oku kusizisa kwingcamango yokuphepha ukuzikhusela komzimba, enye yezona mpawu ziphambili zomhlaza.
Unyango lwe-CAR-T, okanye unyango lweeseli ze-CAR-T, lubandakanya ukwahlula iiseli ze-T zesigulana, ukuzikhulisa ngaphandle komzimba, uze emva koko ungenise i-antigen yeseli ye-tumor eyilwe ngobuchule i-CAR (i-chimeric antigen receptor) kwiiseli ze-T. Emva kokucubungula, umsebenzi we-T lymphocytes wokulwa ne-tumor uphucuka kakhulu ngaphambi kokuba uphinde ufakwe emzimbeni wesigulana, ngaloo ndlela ubuyisela amandla eeseli ze-T okubona nokubulala iiseli zomhlaza. Le yintsingiselo yonyango lweeseli ze-CAR-T.
Unyango lwe-CAR-T lwe-Impact Bio i-IMPT-514 ivunyiwe yi-FDA.
Ngomhla wama-21 ku-Agasti 2024, i-Impact Bio yabhengeza ukuba i-FDA iyivumile isicelo sayo se-IND sonyango lwe-IMPT-514 eyalwenzayo. I-IMPT-514 lunyango lwe-CD19/CD20 CAR-T olune-bispecific olusetyenziselwa ukunyanga i-active refractory systemic lupus erythematosus (SLE). Kwidatha yovavanyo lweklinikhi, i-IMPT-514 ibonakaliswe isebenza kakuhle ekuveliseni izigulana ezine-immunosuppression enzima evela kwizifo ezahlukeneyo ze-autoimmune, kwaye ibonise amandla amakhulu okususa iiseli ze-B ngeprofayili ye-cytokine ethambileyo. Unyango lwe-Axicabtagene ciloleucel CAR-T lwe-B-cell lymphoma enkulu lusabonisa impendulo eqhubekayo emva kweminyaka emihlanu. Ngomhla wesi-2 ku-Agasti 2024, i-American Society of Clinical Oncology (ASCO) ikhuphe ingxelo yedatha malunga namazinga okusinda kwexesha elide emva konyango lweeseli ze-CAR-T. Iziphumo zibonise ukuba phakathi kwezigulane ezifumene unyango lwe-CAR-T, izinga lokusinda elingenayo inkqubela phambili yeminyaka emi-5 yayiyi-29%, izinga lokusinda lilonke leminyaka emi-5 (OS) yayiyi-40%, kwaye izinga lokusinda elikhethekileyo le-lymphoma yeminyaka emi-5 yayiyi-53%, kunye nokubuyela umva okungaqhelekanga kade. I-Axicabtagene ciloleucel lunyango lweseli ye-CAR-T ye-autologous CD19 chimeric antigen receptor oluvunyiweyo kunyango lwe-lymphoma enkulu ye-B-cell ephinde yabuyela okanye enganyangekiyo. Isiphelo: Kwindawo yokhathalelo oluqhelekileyo, iziphumo zonyango ze-axicabtagene ciloleucel CAR-T ziyahambelana neziphumo ezibikwe kwizilingo zeklinikhi, kunye neempendulo ezihlala ixesha elide ezibonwe kumanqaku eminyaka emi-5.
Unyango lokuqala lwe-CAR-T oluphumeleleyo kwihlabathi liphela lwesifo sokuzikhusela komzimba.

Ngomhla wesi-4 kweyeDwarha ngo-2024, iwebhusayithi yeNature yayiphethe ingxelo eyayisazisa iziphumo zophando ezivela kwiqela laseTshayina. Izazinzulu zisebenzise iteknoloji yokuhlela iijini yeCRISPR-Cas9 ukuze zenze ubunjineli kwiiseli zeCAR-T ezisempilweni ezivela kubanikeli ezijolise kwiCD19, ziphuhlisa isizukulwana esitsha sonyango lweCAR-T olupheleleyo oluyi-allogeneic oluncede izigulane ezintathu ezinezifo ezinzima zokuzikhusela komzimba ukuba zifumane uxolelo lwexesha elide.