Ukuchazwa Okuphelele Kokwelashwa Kwe-CAR T-Cell

I-CAR-T (i-Chimeric Antigen Receptor T-Cell), emele ama-chimeric antigen receptor T-cells, inqubo lapho ama-T cell omuntu ehlelwa khona ngokwezakhi zofuzo ngaphandle komzimba ukuze aguqulwe, okuwanikeza ikhono lokubona nokubulala ngempumelelo amaseli omdlavuza ngaphambi kokuba aphinde afakwe emzimbeni wesiguli, ngaleyo ndlela kufezwe umgomo wokwelapha izimila ezinobungozi.
Eqinisweni, ukwelashwa kwe-CAR-T akusetshenziselwa nje ukwelapha umdlavuza kodwa futhi kunamandla amakhulu emikhakheni yezifo ezizimele, izifo ezingamahlalakhona, izifo zenhliziyo, kanye nezifo ezihlobene nokuguga.
Amaseli e-T, aziwa nangokuthi ama-T lymphocyte, ayizingxenye eziyinhloko zama-lymphocyte futhi ngokuyinhloko anesibopho sokusabela komzimba kanye nokuzivikela ezifweni. Anemisebenzi efana nokubulala ngqo amaseli aqondiwe, ukusiza nokuvimbela amaseli e-B ukuthi akhiqize ama-antibodies, ukuphendula kuma-antigen athile nama-mitogens, kanye nokukhiqiza ama-cytokine.
Yiqiniso, isimiso somzimba sokuzivikela somuntu asigcini ngamaseli e-T kuphela; sihlanganisa namaseli e-B, ama-neutrophil, amaseli e-K, amaseli e-NK, nokuningi. Adlala indima ekususeni imikhiqizo ye-metabolic emzimbeni, ekuboneni nasekukhiqizeni ama-antibodies, nasekuboneni nasekubulaleni amagciwane angaphandle kanye namaseli omdlavuza.
Njengoba amaseli e-T kakade enomsebenzi wokuqaphela nokubulala amaseli omdlavuza, kungani kudingeka ukwengeza i-CAR kumaseli e-T ngokwenziwa ukuze kudalwe amaseli e-CAR-T ukuze kubulawe amaseli omdlavuza? Lokhu kusiletha emcabangweni wokugwema amasosha omzimba, okungenye yezimpawu eziyisisekelo zomdlavuza.
Ukwelashwa kwe-CAR-T, noma ukwelashwa kwamaseli e-CAR-T, kuhilela ukuhlukanisa amaseli e-T esiguli, ukuwandisa ngaphandle komzimba, bese kungeniswa i-antigen yeseli lesimila i-CAR (i-chimeric antigen receptor) eklanywe ngokwenziwa kumaseli e-T. Ngemva kokucubungula, umsebenzi wokulwa nesimila wama-T lymphocyte uthuthukiswa kakhulu ngaphambi kokuba uphinde ufakwe emzimbeni wesiguli, ngaleyo ndlela kubuyiselwe ikhono lamaseli e-T lokubona nokubulala amaseli omdlavuza. Lokhu kuyingqikithi yokwelashwa kwamaseli e-CAR-T.
Ukwelashwa kwe-CAR-T kwe-Impact Bio i-IMPT-514 ithola imvume ye-FDA.
Ngo-Agasti 21, 2024, i-Impact Bio yamemezela ukuthi i-FDA isivumile isicelo sayo se-IND sokwelashwa kwe-IMPT-514 eyakusungula. I-IMPT-514 iyindlela yokwelapha ye-CD19/CD20 CAR-T ebili esetshenziselwa ukwelapha i-lupus erythematosus esebenzayo engasebenzi kahle (SLE). Emininingwaneni yokuhlolwa kwemitholampilo, i-IMPT-514 iboniswe isebenza kahle kakhulu ekukhiqizeni iziguli ezine-immunosuppression enzima yezifo ezahlukahlukene zokuzivikela komzimba, futhi ibonise amandla anamandla okususa amaseli e-B ngephrofayili ye-cytokine emnene. Ukwelashwa kwe-Axicabtagene ciloleucel CAR-T kwe-lymphoma enkulu ye-B-cell kusabonisa impendulo eqhubekayo ngemva kweminyaka emihlanu. Ngo-Agasti 2, 2024, i-American Society of Clinical Oncology (ASCO) ikhiphe umbiko wedatha ngamanani okusinda kwesikhathi eside ngemuva kokwelashwa kwamaseli e-CAR-T. Imiphumela ikhombisile ukuthi phakathi kweziguli ezithole ukwelashwa kwe-CAR-T, izinga lokusinda elingenayo inqubekela phambili yeminyaka emi-5 lalingu-29%, izinga lokusinda lilonke leminyaka emi-5 (OS) lalingu-40%, kanti izinga lokusinda eliqondene ne-lymphoma yeminyaka emi-5 lalingu-53%, kanye nokubuyela emuva okungavamile sekwephuzile. I-Axicabtagene ciloleucel iwukwelashwa kweseli le-CAR-T eliyi-autologous CD19 chimeric antigen receptor elivunyelwe ukwelashwa kwe-lymphoma enkulu ye-B-cell ephinde yabuyela emuva noma engaphikisi. Isiphetho: Esimweni sokunakekelwa okujwayelekile, imiphumela yokwelashwa kwe-axicabtagene ciloleucel CAR-T iyahambisana nemiphumela ebikwe ezivivinyweni zemitholampilo, ngezimpendulo eziqhubekayo nezihlala isikhathi eside ezibonwe eminyakeni emi-5.
Ukwelashwa kokuqala kwe-CAR-T okuphumelele emhlabeni kwesifo sokuzivikela komzimba.

Ngo-Okthoba 4, 2024, iwebhusayithi ye-Nature yakhipha umbiko oveza umphumela wocwaningo oluvela eqenjini laseShayina. Ososayensi basebenzise ubuchwepheshe bokuhlela izakhi zofuzo be-CRISPR-Cas9 ukuze baklame izakhi zofuzo amaseli e-CAR-T anempilo asuselwa kubaxhasi ahlose i-CD19, bathuthukisa isizukulwane esisha sokwelashwa kwe-CAR-T okujwayelekile kwe-allogeneic okwasiza iziguli ezintathu ezinezifo ezinzima zokuzivikela komzimba ukuthi zifinyelele ukuphulukiswa kwesikhathi eside.