Ukulawula Iingxaki Zexesha Elide Zonyango lweCAR-T: Ingcaciso Evela Kumhlaza Wendalo

Unyango lweeseli zeChimeric Antigen Receptor (CAR)-T lutshintshe kakhulu unyango lwe-hematologic moldancies, enika ithemba kwizigulana ezinezifo ezinganyangekiyo. Nangona kunjalo, iingxaki zexesha elide ezifana nosulelo kunye nezifo zesibini zomhlaza ziseyingxaki enkulu yokhuseleko, ngokutsho kwenqaku lakutshanje kwi Umhlaza wendalo.

Unyango lwe-CAR-T lwaqala ukusetyenziswa ngokubanzi ngenxa yokusebenza kwalo okumangalisayo kwizilingo zeklinikhi kunye nokusetyenziswa kwihlabathi lokwenyani. Nangona izinto ezinobuthi ezinje nge-cytokine release syndrome (CRS) kunye ne-immune effector cell-associated neurotoxicity syndrome (ICANS) ziye zalawuleka ngokuqhubela phambili kunyango oluxhasayo, uhlalutyo lwakutshanje lugxininisa ukuxhaphaka kokufa okungabuyeliyo (NRM) ngenxa yosulelo kunye nomhlaza wesibini phakathi kwabaphenduli be-CAR-T.

Uhlalutyo lwe-meta olubandakanya i-7,604 lymphoma kunye I-Multiple Myeloma Izigulane ezenze unyango lwe-CAR-T zibonakalise izinga le-NRM lilonke le-6.8%, lahluka ngokwezifo ezahlukeneyo kunye nokwakheka kwe-CAR-T.Iintsholongwane zibangele uninzi lwamatyala e-NRM, enganxulumananga ne Imveliso ye-CAR-T okanye isifo esisisiseko. Nangona impembelelo ebalulekileyo ye-COVID-19 ngexesha lophando, usulelo lwebhaktiriya kunye nefungus ngalunye lube negalelo kwi-20% yokufa okunxulumene nosulelo. La manani ayafana nalawo abonwe emva kokufakelwa kweeseli ze-stem ze-hematopoietic autologous (auto-HSCT).

Ukuze kuncitshiswe le mingcipheko, abaphandi bagxininisa ukusetyenziswa kwezixhobo zokuqikelela ezifana ne-CAR-HEMATOTOX score, evavanya izinto ezifana ne-hematopoietic reserve kunye ne-baseline inflammation. Le nkqubo yokubeka amanqaku inceda ekuchongeni izigulana ezisengozini ephezulu ezinokuxhamla kwii-antibiotics zokuthintela ezilungiselelweyo kunye nokujonga ngokukhuselekileyo amasosha omzimba. Okuphawulekayo kukuba, i-severe immune effect cell-associated hematotoxicity (ICAHT) inxulumene nezinga eliphezulu le-NRM (14% xa kuthelekiswa ne-4.5% kwiimeko ezingezizo ezinzulu).

Iingxaki zesibini zomhlaza, kuquka i-myelodysplastic syndromes (MDS), i-acute myeloid leukemia (AML), kunye ne-carcinomas, zimele enye ingxaki ebalulekileyo. Ezi zifo zomhlaza zinxulunyaniswa kakhulu nonyango olunzima lwangaphambili olufana ne-chemotherapy kunye ne-auto-HSCT endaweni yemveliso ye-CAR-T ngokwayo. I-Clonal hematopoiesis, eyandulela i-MDS/AML enxulumene nonyango, ibonwe kwizigulane ezifikelela kwi-56% ngaphambi kokufakwa kwe-CAR-T.

Indima yonyango lwe-CAR-T kwezi zifo zomhlaza isaphandwa. Nangona amatyala e-CAR-T ebangelwe yi-CAR-T abangelwa yi-CAR-T. I-T-Cell Lymphoma Kuye kwaxelwa kwangaphambili ukuba yintoni imbangela, ubudlelwane obubangela le ngxaki abuqinisekanga. Kwimeko enye ephawulekayo, amanqanaba aphezulu e-CAR-RNA afunyenwe kunyango lwe-T-cell lymphoma emva kwe-CAR-T, kodwa uhlalutyo lwe-genetic aluzange lubonise ukuba ukufakwa kwe-CAR yeyona nto iphambili ebangela umhlaza.

Amaqhinga okuLawula iiNgozi
Ukuze kuphuculwe iprofayili yomngcipheko wenzuzo yonyango lwe-CAR-T, abaphandi bacebisa ukungenelela kwangethuba kwizigulane ezineendlela ezimbalwa zonyango lwangaphambili ukuze kuncitshiswe ubuthi obuqokelelweyo. Iinkqubo zokubeka amanqaku kwangaphambili kunye nokulandelwa kwexesha elide kwabafumana i-CAR-T kunokuphucula ukhuseleko ngokuvumela ukufunyanwa kwangethuba kunye nokulawulwa kweengxaki.

Eli nqaku ligxininisa ukubaluleka kokuxela ngeziganeko ezingalunganga ngokupheleleyo kwiimvavanyo zeklinikhi nakwiirejista, ingakumbi kwiintsholongwane, ii-malignancies zesibini, kunye ne-NRM. Olu lwazi luya kunceda oogqirha ukuba baphucule iindlela zonyango kunye neendlela zokukhetha izigulana.

Isiphelo
Nangona unyango lwe-CAR-T lunika amandla okunyanga angenakuthelekiswa nanto kwizifo zegazi, ukulawula iingozi zalo zexesha elide kubalulekile. Uphando lwexesha elizayo lufanele lugxile ekuphuculeni izixhobo zokuqikelela kunye nokuphonononga ezinye iindlela zonyango kwizigulane ezindala okanye ezibuthathaka ezisenokunganyamezelani kakuhle neetyhefu ezinxulumene ne-CAR-T.

Lo msebenzi uphambili usebenza njengesikhumbuzo sesidingo esiqhubekayo sokulinganisela ukusebenza kakuhle kunye nokhuseleko kunyango olutsha, ukuqinisekisa iziphumo ezilungileyo kwizigulana kwihlabathi liphela.