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 ukukhusela umzimba. Enye yeeseli ezibalulekileyo ezibandakanyekayo ziiseli ezimhlophe zegazi, ezikwabizwa ngokuba zii-leukocytes, eziza kwiindidi ezimbini ezisisiseko ezidibanayo ukufuna nokutshabalalisa izinto eziphilayo okanye izinto ezibangela izifo.
Iindidi ezimbini ezisisiseko zee-leukocytes zezi:
Ø ii-phagocytes, iiseli ezihlafuna izinto eziphilayo ezihlaselayo
Ø ii-lymphocytes, iiseli ezivumela umzimba ukuba ukhumbule kwaye uqaphele abahlaseli bangaphambili kwaye bancede umzimba ukuba ubatshabalalise
Iiseli ezahlukeneyo zithathwa njengee-phagocytes. Uhlobo oluqhelekileyo yi-neutrophil, elwa kakhulu neebhaktheriya. Ukuba oogqirha bakhathazekile ngentsholongwane ebangelwa yintsholongwane, banokuyalela uvavanyo lwegazi ukuze babone ukuba isigulana sinenani elandayo lee-neutrophils ezibangelwa yintsholongwane. Ezinye iintlobo ze-phagocytes zinemisebenzi yazo ukuqinisekisa ukuba umzimba usabela ngokufanelekileyo kuhlobo oluthile lomhlaza.
Iintlobo ezimbini ze-lymphocytes zii-B lymphocytes kunye nee-T lymphocytes. Ii-lymphocytes ziqala kwi-bone mongo kwaye zihlala apho zize zikhule zibe zii-B cells, okanye zihambe ziye kwi-thymus gland, apho zikhula zibe zii-T cells. Ii-B lymphocytes kunye nee-T lymphocytes zinemisebenzi eyahlukileyo: Ii-B lymphocytes zifana nenkqubo yomzimba yobukrelekrele bomkhosi, zifuna iithagethi zazo kwaye zithumela ukhuselo ukuba luzivalele. Ii-T cells zifana namajoni, zitshabalalisa abahlaseli abachongiweyo yinkqubo yobukrelekrele.
Inkqubo yomzimba yokuzikhusela yenziwe luthungelwano lweeseli, izicubu, kunye namalungu asebenzisanayo ukukhusela umzimba. Enye yeeseli ezibalulekileyo ezibandakanyekayo ziiseli ezimhlophe zegazi, ezikwabizwa ngokuba zii-leukocytes, eziza kwiindidi ezimbini ezisisiseko ezidibanayo ukufuna nokutshabalalisa izinto eziphilayo okanye izinto ezibangela izifo.
Iindidi ezimbini ezisisiseko zee-leukocytes zezi:
Ø ii-phagocytes, iiseli ezihlafuna izinto eziphilayo ezihlaselayo
Ø ii-lymphocytes, iiseli ezivumela umzimba ukuba ukhumbule kwaye uqaphele abahlaseli bangaphambili kwaye bancede umzimba ukuba ubatshabalalise
Iiseli ezahlukeneyo zithathwa njengee-phagocytes. Uhlobo oluqhelekileyo yi-neutrophil, elwa kakhulu neebhaktheriya. Ukuba oogqirha bakhathazekile ngentsholongwane ebangelwa yintsholongwane, banokuyalela uvavanyo lwegazi ukuze babone ukuba isigulana sinenani elandayo lee-neutrophils ezibangelwa yintsholongwane. Ezinye iintlobo ze-phagocytes zinemisebenzi yazo ukuqinisekisa ukuba umzimba usabela ngokufanelekileyo kuhlobo oluthile lomhlaza.
Iintlobo ezimbini ze-lymphocytes zii-B lymphocytes kunye nee-T lymphocytes. Ii-lymphocytes ziqala kwi-bone mongo kwaye zihlala apho zize zikhule zibe zii-B cells, okanye zihambe ziye kwi-thymus gland, apho zikhula zibe zii-T cells. Ii-B lymphocytes kunye nee-T lymphocytes zinemisebenzi eyahlukileyo: Ii-B lymphocytes zifana nenkqubo yomzimba yobukrelekrele bomkhosi, zifuna iithagethi zazo kwaye zithumela ukhuselo ukuba luzivalele. Ii-T cells zifana namajoni, zitshabalalisa abahlaseli abachongiweyo yinkqubo yobukrelekrele.
Iteknoloji ye-T cell ye-Chimeric antigen receptor (CAR): luhlobo lwe-adoptive cellular immunotherapy (ACI). I-T cell yesigulane iveza i-CAR ngeteknoloji yokwakha kwakhona izakhi zofuzo, ezenza ii-T cells ezisebenza kakuhle zijoliswe ngakumbi, zibulale kwaye ziqhubeke kuneeseli zomzimba eziqhelekileyo, kwaye zinokoyisa indawo encinci yokuthintela ukuvuvukala kwamathumbu kunye nokuphelisa ukunyamezelana kwamasosha omzimba. Olu lunyango oluthile lwe-immune cell anti-tumor.
Umgaqo we-CART kukukhupha "inguqulelo eqhelekileyo" yeeseli ze-T zomzimba zesigulana kunye nokuqhubela phambili ubunjineli be-gene, ukuhlanganisa kwi-vitro ukuze kujoliswe kwiithagethi ezithile ze-tumor zesixhobo esikhulu se-antipersonnel "i-chimeric antigen receptor (CAR)", uze emva koko ufake iiseli ze-T ezitshintshileyo emzimbeni wesigulana, ii-receptors ezintsha zeseli eziguquliweyo ziya kufana nokufaka inkqubo ye-radar, ekwaziyo ukukhokela iiseli ze-T ukufumana nokutshabalalisa iiseli zomhlaza.
Inzuzo yeNQAKU kwi-BPIH
Ngenxa yokwahluka kwendlela ezisebenza ngayo iimpawu ze-intracellular signal domain, i-CAR iphuhlise izizukulwana ezine. Sisebenzisa isizukulwana samva nje se-CART.
1stisizukulwana: Bekukho icandelo elinye kuphela lesignali yangaphakathi kweseli kwaye isiphumo sokuthintela ithumba besibi.
2ndisizukulwana: Kongezwe imolekyuli ekhuthazayo ngokusekelwe kwisizukulwana sokuqala, kwaye amandla eeseli ze-T okubulala iithumba aphuculwe.
3rdisizukulwana: Ngokusekelwe kwisizukulwana sesibini se-CAR, amandla eeseli ze-T okuthintela ukwanda kwethumba kunye nokukhuthaza i-apoptosis aphuculwe kakhulu.
4thisizukulwana: Iiseli ze-CAR-T zinokubandakanyeka ekususweni kwenani leeseli zethumba ngokusebenzisa i-downstream transcription factor NFAT ukuze ibangele i-interleukin-12 emva kokuba i-CAR iqaphele i-antigen ekujoliswe kuyo.
Inkqubo yonyango
1) Ukwahlulwa kweeseli ezimhlophe zegazi: Iiseli ze-T zesigulana zahlulwe kwigazi elingaphandle;
2) Ukusebenza kwee-T cells: ii-magnetic beads (ii-artificial dendritic cells) ezigqunywe ngee-antibodies zisetyenziselwa ukusebenza kwee-T cells;
Ukudluliselwa kwe-transfection: Iiseli ze-T zenziwe ngokwemfuza ukuze zivelise i-CAR kwi-vitro.
3) Ukwandisa: Iiseli ze-T eziguqulwe ngokwemfuza ziyandiswa kwi-vitro.
4) Unyango lweKhemotherapy: Isigulana sinyangwa kwangaphambili ngekhemotherapy ngaphambi kokuba kufakwe kwakhona iiseli ze-T;
5) Ukuphinda kufakwe: Iiseli ze-T eziguqulwe ngokwemfuza ziphinda zingene kwisigulana.
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-tumor antigens. Unyango lwe-CAR T aluthintelwanga zii-protein antigens zeeseli ze-tumor. I-CAR T ingasebenzisa ii-sugar kunye ne-lipid non-protein antigens zeeseli ze-tumor ukuchonga ii-antigens kwiinkalo ezahlukeneyo.
4)I-CAR-T inokuphinda-phinda okubanzi. Ekubeni iindawo ezithile zibonakaliswa kwiiseli ezininzi ze-tumor, 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 ukuthintela ukuphinda kuvele isifo somhlaza.