Unyango lwe-CAR-T: Ikamva Elithembisayo Leengxaki Zeeseli ze-T
Unyango lweChimeric Antigen Receptor T-cell (CAR-T) luye lwaguqula unyango lwe-B-cell monoancies, lubonelela ngonyango oluhlala ixesha elide kwanonyango kwizigulane ezininzi. Bekhuthazwa yile mpumelelo, abaphandi bagxile ekusebenziseni i-CAR-T kwi-T-cell monoancies, kuquka I-T-Cell Lymphomas (TCL) kunye ne-T-cell acute lymphoblastic leukemia (T-ALL). Nangona kunjalo, le mihlaza ye-T-cell inika imingeni eyahlukileyo kuphuhliso lonyango lwe-CAR-T.
Ii-T-cell malignancies, ezibangela inxalenye enkulu yomhlaza wobuntwana nowabantu abadala, zaziwa ngokuba nolaka nokunganyamezelani nonyango oluqhelekileyo. I-T-ALL kunye ne-TCL zahlukene kakhulu, zineziphumo ezimbi kwiindawo ezibuyela umva okanye ezingavumiyo (r/r), nto leyo egxininisa isidingo esingxamisekileyo sonyango olutsha. Unyango lwe-CAR-T lomhlaza we-T-cell lufumene ingqwalasela enkulu ngenxa yamandla alo okubonelela ngesisombululo esijolise kuso nesisebenzayo.
Umngeni ukho ekubonakalisweni okwahlukeneyo kweenjongo ze-antigen phakathi kwee-T-cells ezinobungozi kunye nee-T-cells eziqhelekileyo, okunokukhokelela kwi-"fratricide," apho ii-CAR-T cells zitshabalalisa ii-T-cells eziphilileyo ngengozi. Ukongeza, i-T-cell aplasia, enokushiya izigulana zisengozini yosulelo, ibeka omnye umngcipheko omkhulu. Nangona le miqobo, inkqubela phambili yeklinikhi yakutshanje ibonise iziphumo ezithembisayo ze-CAR-T kwi-T-ALL kunye ne-TCL.
Uphononongo lwakutshanje olupapashwe kwi Ukuqhubela phambili kwegazi Igxininisa uvavanyo lweklinikhi oluthembisayo. Enye indlela ibandakanya ukujolisa kwi-CD7, iproteni ebonakala kumphezulu we-T-ALL kunye nee-lymphomas ezithile ze-T-cell. Kwizilingo zokuqala, unyango lwe-CAR-T olujoliswe kwi-CD7 lubonakalise ukusebenza okumangalisayo, lufezekisa ukukhululwa ngokupheleleyo kwizigulane ezininzi. Ukongeza, amaqhinga ajolise ekunciphiseni "i-fratricide" kunye nokuphucula ukuveliswa kweeseli ze-CAR-T avula indlela yokuphumelela kwezonyango.
Izilingo zakutshanje ziye zazama nokuhlela ii-T-cells ukuphucula ukuchaneka kunye nokuqina kwee-CAR-T cells. Umzekelo, ukusetyenziswa kwetekhnoloji ye-CRISPR-Cas9 ukujolisa kwii-antigens ezithile ezifana ne-CD5, i-CD7, kunye ne-TRBC kubonise amandla okuphucula ukhuseleko kunye nokusebenza kakuhle. Iziphumo zokuqala zibonisa ukuba unyango lwe-CAR-T, xa lucwangciswe ngononophelo, lunokuba sisixhobo esinamandla sokulwa nomhlaza wee-T-cell.
Ngaphezu koko, ukudibanisa unyango lwe-CAR-T kunye nezinye iindlela zonyango, ezifana nokufakelwa kweeseli ze-hematopoietic stem cell (allo-HSCT), kubonise ithemba ekwandiseni ukusinda kunye nokuthintela ukubuyela umva. Kwilingo lesigaba sesiBini sonyango lwe-CAR-T olujoliswe kwi-CD7, ama-63.5% ezigulana ahlala ekhululekile emva kweminyaka emibini, kwaye abo bafumana i-allo-HSCT baphucule kakhulu ukusinda okungenankqubela phambili (PFS).
Njengoko uphando luqhubeka, imeko yonyango lwe-CAR-T kwi-T-cell monoancies ibonakala inethemba ngakumbi. Nangona kusekho imingeni ebalulekileyo ekufuneka iyoyiswe, kuquka ukulawula i-severe cytokine release syndrome (CRS) kunye ne-neurotoxicity, ukuqonda okukhulayo kwetekhnoloji ye-CAR-T kuyaqhubeka nokwandisa ukusetyenziswa kwayo okunokwenzeka.
Apha kwi-BIOOCUS, sizibophelele ekubeni phambili kuphuhliso lonyango lwe-CAR-T kwaye sivuya ukubonelela ngolu nyango luphambili kwizigulana kwihlabathi liphela. Njengoko uvavanyo lwezonyango luqhubeka lutshintsha, sinethemba lokuba unyango lwe-CAR-T ngenye imini luya kubonelela ngokhetho lokunyanga abo banesifo se-T-cell malignancies, nto leyo eza kuzisa ithemba elitsha kwizigulana nakwiintsapho ezifuna iindlela zonyango ezisebenzayo.
Ukuze ufumane ulwazi oluthe kratya malunga neenkqubo zethu zonyango lwe-CAR-T, ndwendwela iwebhusayithi yethu okanye unxibelelane neqela lethu lenkxaso yezigulane.