Ukukhawulezisa Ukulungiswa Kweeseli ze-CAR-T Ukuphucula Iziphumo Zezigulane

Unyango lweeseli ze-CAR-T, unyango oluguqula izinto I-B-Cell Leukemia kunye ne-lymphoma, iphandwa ngakumbi kwezinye iintlobo zomhlaza wegazi, iithumba eziqinileyo, kunye neengxaki zokuzikhusela komzimba. Nangona kunjalo, ukwandisa olu nyango kwiimpawu ezintsha kuveza imingeni yezothutho, njengoko ukuveliswa kweeseli ze-CAR-T okwangoku kungathatha iiveki ezi-3-6. Uphononongo lwakutshanje kwiI-Lancet Haematology ixoxa ngenkqubela phambili ebalulekileyo ekuvelisweni kweeseli zeCAR-T ezijolise ekwenzeni lula iinkqubo, ukuphucula umgangatho weeseli, kunye nokwandisa ukufikelela kwezigulane.

Ngokwesiko, ukulungiswa kweeseli ze-CAR-T kufuna ukuvuselelwa nokwandiswa kweeseli kwi-vitro, nto leyo enokubangela ukudinwa kweeseli kunye nokusebenza kakuhle konyango okunciphileyo. Izinto ezintsha zamva nje, ezifana neenkqubo zokwandiswa okunciphileyo, iindlela zokungasebenzisi, kunye nemveliso yokhathalelo, zibonelela ngotshintsho olukhawulezileyo olunolawulo oluncinci kwi-vitro. Ezi ndlela, ngoku zisetyenziswa kuvavanyo lweklinikhi nakwimisebenzi yorhwebo. Iimveliso ze-CAR-T, kugxininiswa ekuvelisweni kweeseli ze-CAR-T ezingahlukanga kangako nezinganyangekiyo kukudinwa, nto leyo ekhokelela kunyango olunokubonelela ngemiphumo ehlala ixesha elide yokulwa nethumba.

Olu phononongo lukwagxininisa inkqubela phambili ekukhethweni kwangaphambili kweeseli ze-T ukususa iiseli ezingafunekiyo okanye ezithintela amasosha omzimba, nto leyo ephucula amandla okunyanga eemveliso ze-CAR-T. Iindlela zobuchule eziphucula ixesha le-leukapheresis ngokusekelwe kwiziphumo zegazi zangaphambi konyango ziphucula ngakumbi ukusebenza kakuhle kwezixhobo kunye nokufikeleleka kwazo.

Iinkqubo zokulungiselela i-CAR-T ngokukhawuleza sele zibonisa iziphumo ezithembisayo. Uvavanyo lwezonyango lubonisa ukuba amaxesha amafutshane okuvelisa anokukhokelela ekuphuculeni ukuqina nokusebenza kakuhle kweeseli, kunye nezifundo eziqhubekayo ezihlola iindlela zokwenza iimveliso ezikhawulezayo kakhulu ezizisa iiseli ze-CAR-T kwizigulana ngosuku olunye.

Ukongeza kwiindlela zokunciphisa ukwanda, ubunjineli beeseli ezintsha buphucula ukusebenza kwe-CAR-T. Iindlela ziquka ukusetyenziswa kwezithinteli zemolekyuli ezincinci ngexesha lokwenziwa ukuze kugcinwe iimpawu zememori ye-T-cell kunye nokumelana nokudinwa. Umzekelo, izithinteli ze-AKT zidityaniswa kwiiprotokholi zemveliso ye-CAR-T, zibonisa umsebenzi ophuculweyo wokulwa nethumba kwiimodeli ze-leukemia zangaphambi kweklinikhi. Ngaphezu koko, iiseli ze-CAR-T ezenzelwe ukukhupha ii-cytokines ezivuselela amasosha omzimba, ezifana ne-IL-18, zibonisa ulawulo oluphezulu lwethumba emzimbeni kwaye ziyaqhubeka nokukhula kweeseli kwizilingo zeklinikhi zesigaba sokuqala.

Njengoko imfuno yehlabathi yonyango lwe-CAR-T ikhula, olu phuculo luzisa amandla okuguqula ukhathalelo lwezigulane, okwenza unyango olusebenzayo lufikeleleke ngokukhawuleza nangomlinganiselo omkhulu.