Yintoni i-CAR-T (i-Chimeric Antigen Receptor T-cell)?
Okokuqala, makhe sijonge inkqubo yomzimba yokuzikhusela kwizifo.
Inkqubo yomzimba yokuzikhusela yenziwe luthungelwano lweeseli, izicubu, kunye namalungu asebenzisanayo ukuzekhusela umzimba. Enye yeeseli ezibalulekileyo ezibandakanyekayo ziiseli ezimhlophe zegazi, ezikwabizwa ngokuba zii-leukocytes,eziza ngeentlobo ezimbini ezisisiseko ezidibanayo ukufuna nokutshabalalisa izinto eziphilayo ezibangela izifo okanyeizinto.
Iindidi ezimbini ezisisiseko zee-leukocytes zezi:
Iiphagocytes, iiseli ezihlafuna izinto eziphilayo ezihlaselayo.
Ii-lymphocytes, iiseli ezivumela umzimba ukuba ukhumbule kwaye uqaphele abahlaseli bangaphambili kwaye bancedeumzimba uyabatshabalalisa.
Iiseli ezahlukeneyo zithathwa njengee-phagocytes. Uhlobo oluqhelekileyo yi-neutrophil,elwa kakhulu neentsholongwane. Ukuba oogqirha bakhathazekile ngentsholongwane, banokuyalelauvavanyo lwegazi ukuze kubonwe ukuba isigulana sinenani elandayo lee-neutrophils ezibangelwa lusulelo.
Ezinye iintlobo ze-phagocytes zinemisebenzi yazo ukuqinisekisa ukuba umzimba uphendula ngokufanelekileyokuhlobo oluthile lomhlaseli.
Iintlobo ezimbini ze-lymphocytes yi-B lymphocytes kunye ne-T lymphocytes. Ii-lymphocytes ziqalakwi-bone mongo kwaye zihlale apho zize zikhule zibe zii-B cells, okanye zishiye ziye kwi-thymusi-gland, apho zikhula khona zibe zii-T cells. Ii-B lymphocytes kunye nee-T lymphocytes zahlukileimisebenzi: Ii-B lymphocytes zifana nenkqubo yobukrelekrele bomkhosi womzimba, zifunaiithagethi kunye nokuthumela ukhuselo ukuba luvale kuzo. Ii-T cells zifana namajoni, zitshabalalisaabahlaseli abachongiweyo yinkqubo yezobuntlola.
Iteknoloji ye-Chimeric antigen receptor (CAR) T cell: luhlobo lweseli elamkelweyounyango lwe-immunotherapy (ACI). Iiseli ze-T zesigulana ziveza i-CAR ngokwakhiwa kwakhona kwemfuzaubuchwepheshe, obenza ii-T cells ezisebenza kakuhle zijoliswe ngakumbi, zibulale kwaye ziqhubekeka kunokubaiiseli zomzimba eziqhelekileyo, kwaye zinokoyisa imeko-bume yokuthintela amajoni omzimba yendawoUkunyamezelana komzimba nethumba kunye nokwaphuka. Olu lunyango oluthile lokulwa nomhlaza olusetyenziswa kwiiseli zomzimba.
Umgaqo we-CART kukususa "inguqulelo eqhelekileyo" yeeseli ze-T zomzimba zesigulana.kwaye uqhubeke nobunjineli bezakhi zofuzo, udibanise kwi-vitro ukuze ufumane iithagethi ezithile zethumba ezinkuluisixhobo sokulwa nabasebenzi "i-chimeric antigen receptor (CAR)", size emva koko sifake iiseli ze-T ezitshintshileyoxa zibuyela emzimbeni wesigulana, ii-receptors ezintsha zeeseli eziguquliweyo ziya kufana nokufaka inkqubo yeradar,ekwaziyo ukukhokela ii-T cells ukuba zifumane kwaye zitshabalalise iiseli zomhlaza.
Inzuzo yeNQAKU kwi-BPIH
Ngenxa yokwahluka kwisakhiwo se-intracellular signal domain, i-CAR iphuhlise ezineizizukulwana. Sisebenzisa iNQOLO yesizukulwana samva nje.
1stisizukulwana: Kwakukho icandelo elinye kuphela lesignali yangaphakathi kweseli kunye nokuthintela ithumbaisiphumo besibi.
2ndisizukulwana: Kongezwe imolekyuli ekhuthazayo ngokusekelwe kwisizukulwana sokuqala, kwayeAmandla eeseli ze-T okubulala iithumba aphuculwe.
3rdisizukulwana: Ngokusekelwe kwisizukulwana sesibini se-CAR, amandla eeseli ze-T okuthintela ithumbaukwanda kunye nokukhuthaza i-apoptosis kuphuculwe kakhulu.
4thisizukulwana: Iiseli ze-CAR-T zinokubandakanyeka ekususweni kwenani leeseli zethumba ngokusebenzisaisebenze i-downstream transcription factor NFAT ukuze ibangele i-interleukin-12 emva kwe-CARiyaziqonda i-antigen ekujoliswe kuyo.
| Isizukulwana | Ukukhuthaza I-Factor | Uphawu |
| 1st | CD3ζ | Ukusebenza kweeseli ze-T ezithile, iiseli ze-T ezinobungozi, kodwa azikwazanga ukwanda nokusinda emzimbeni. |
| 2nd | CD3ζ+CD28/4-1BB/OX40 | Yongeza i-costimulator, phucula ubuthi beeseli, amandla okukhula alinganiselwe. |
| 3rd | CD3ζ+CD28/4-1BB/OX40+CD134/CD137 | Yongeza ii-costimulators ezimbini, uphuculeamandla okwanda kunye nobutyhefu. |
| 4th | I-gene yokuzibulala/i-Amored CAR-T (12IL) Yiya kwi-CAR-T | Hlanganisa i-suicide gene, i-express immune factor kunye nezinye iindlela zokulawula ezichanekileyo. |
Inkqubo yonyango
1) Ukwahlulwa kweeseli ezimhlophe zegazi: Iiseli ze-T zesigulana zahlulwe kwigazi elingaphandle.
2) Ukusebenza kwee-T cells: ii-magnetic beads (iiseli ze-dendritic zokwenziwa) ezigqunywe ngee-antibodies ziisetyenziselwa ukwenza ii-T cells zisebenze.
3) Ukudluliselwa kwe-transfection: Iiseli ze-T zenziwe ngokwezakhi zofuzo ukuze zivelise i-CAR kwi-vitro.
4) Ukwandisa: Iiseli ze-T eziguqulwe ngokwemfuza ziyandiswa kwi-vitro.
5) I-Chemotherapy: Isigulana sinyangwa kwangaphambili nge-chemotherapy ngaphambi kokuba kufakwe kwakhona iiseli ze-T.
6) Ukuphinda kufakwe: Iiseli ze-T eziguqulwe ngokwemfuza ziphinda zingene kwisigulana.
Iimpawu
Iimpawu ze-CAR-T
Inkqubo yokuphefumla: Umhlaza wemiphunga (umhlaza weseli encinci, umhlaza weseli ekrwada,i-adenocarcinoma), umhlaza we-nasopharynx, njl.
Inkqubo yokugaya ukutya: Umhlaza wesibindi, isisu kunye nomhlaza we-colorectal, njl.
Inkqubo yomchamo: I-Kidney kunye ne-adrenal carcinoma kunye ne-metastatic cnacer, njl.
Inkqubo yegazi: I-leukemia ye-lymphoblastic ebukhali nengapheliyo (i-T lymphoma)ngaphandle) njl. njl.
Eminye imhlaza: I-melanoma enobungozi, umhlaza webele, i-prostate kunye nomhlaza wolwimi, njl.
Utyando lokususa isilonda sokuqala, kodwa amandla okuzikhusela aphantsi, kwaye unyango luhamba kancinci.
Iithumba ezine-metastasis ebanzi ezingakwazi ukuqhubeka notyando.
Isiphumo esibi se-chemotherapy kunye ne-radiotherapy sikhulu okanye asikhathali kwi-chemotherapy kunye ne-radiotherapy.
Ukuthintela ukuphinda kuvele ithumba emva kotyando, i-chemotherapy kunye ne-radiotherapy.
Iingenelo
1) Iiseli ze-CAR T zijoliswe kakhulu kwaye zinokubulala iiseli ze-tumor ezine-antigen ekhethekileyo ngempumelelo ngakumbi.
2) Unyango lweeseli ze-CAR-T lufuna ixesha elincinci. I-CAR T ifuna ixesha elifutshane lokukhulisa iiseli ze-T kuba ifuna iiseli ezimbalwa phantsi kwesiphumo esifanayo sonyango. Umjikelo wokukhulisa iiseli ze-vitro ungancitshiswa ube ziiveki ezi-2, nto leyo eyanciphisa kakhulu ixesha lokulinda.
3) I-CAR ayinakukwazi ukubona kuphela ii-peptide antigens, kodwa nee-sugar kunye ne-lipid antigens, yandisa uluhlu olujoliswe kuzo lwee-antigens ze-tumor. Unyango lwe-CAR T alukhawulelwanga zii-protein antigens zeeseli ze-tumor. I-CAR T ingasebenzisa ii-antigens zeswekile kunye ne-lipid ezingezizo iiproteni zeeseli ze-tumor ukuchonga ii-antigens kwiinkalo ezahlukeneyo.
4) I-CAR-T inokuphinda-phinda okubanzi. Ekubeni iindawo ezithile zibonakaliswa kwiiseli ezininzi zethumba, njenge-EGFR, i-CAR gene yale antigen ingasetyenziswa kakhulu xa sele yenziwe.
5) Iiseli ze-CAR T zinomsebenzi wokukhusela umzimba kwaye zinokuphila ixesha elide emzimbeni. Kubaluleke kakhulu kwiklinikhi ukuthintela ukuphinda kuvele ithumba.