Yintoni i-CAR-T (i-Chimeric Antigen Receptor T-cell)?
Okokuqala, makhe siqwalasele inkqubo yomzimba yokuzikhusela kwizifo.
Ukhuselo lomzimba lwenziwe luthungelwano lweeseli, izicubu, kunye namalungu asebenza kunyekhusela umzimba.Enye yeeseli ezibalulekileyo ezibandakanyekayo ziiseli ezimhlophe zegazi, ezikwabizwa ngokuba yi-leukocytes,eziza kwiindidi ezimbini ezisisiseko ezidibanisa ukukhangela nokutshabalalisa izinto eziphilayo ezibangela izifo okanyeizinto.
Iintlobo ezimbini ezisisiseko ze-leukocytes zezi:
Phagocytes, iiseli ezihlafuna izinto eziphilayo ezihlaselayo.
I-Lymphocytes, iiseli ezivumela umzimba ukuba ukhumbule kwaye uqaphele abahlaseli bangaphambili kunye nokuncedaumzimba uyawatshabalalisa.
Inani leeseli ezahlukeneyo zithathwa njenge-phagocytes.Olona hlobo luqhelekileyo yi-neutrophil,nto leyo ilwa iibhaktheriya.Ukuba oogqirha banexhala malunga nosulelo lwebhaktheriya, banokuyalelauvavanyo lwegazi ukubona ukuba isigulana sinenani elongeziweyo lee-neutrophils ezibangelwa lusulelo.
Ezinye iintlobo ze-phagocytes zinemisebenzi yazo yokuqinisekisa ukuba umzimba uphendula ngokufanelekileyokudidi oluthile lomhlaseli.
Ezi ntlobo zimbini ze-lymphocytes yi-B lymphocytes kunye ne-T lymphocytes.Ii-lymphocyte ziqalakumongo wethambo kwaye mhlawumbi uhlale apho kwaye uvuthwe kwiiseli ze-B, okanye ushiye i-thymusidlala, apho zikhula zibe zii-T cells.I-B lymphocytes kunye ne-T lymphocytes zineendawo ezahlukeneyoimisebenzi: B lymphocytes zifana nenkqubo yengqondo yomkhosi umzimba, efuna zaboiithagethi kunye nokuthumela izikhuselo ukutshixa kuzo.Iiseli ze-T zifana namajoni, zitshabalalisaabahlaseli abachongwe yinkqubo yezobuntlola.
I-Chimeric antigen receptor (CAR) itekhnoloji yeseli ye-T: luhlobo lweselula olwamkelekileyoimmunotherapy (ACI).Iseli ye-T yesigulana ivakalisa i-CAR ngokwakhiwa ngokutsha kwemfuzaitekhnoloji, eyenza iiseli ze-T ze-effector zijolise ngakumbi, zibulale kwaye ziqhube ngaphezuiiseli zokhuselo lomzimba, kwaye inokoyisa i-microenvironment yengingqi ye-immunosuppressive yeithumba kunye nekhefu host ukunyamezelana omzimba.Olu lunyango oluthile lwe-immune cell anti - tumor.
Umgaqo we-CART kukuthatha "uguqulelo oluqhelekileyo" lweeseli T zesigulanakwaye uqhubeke nobunjineli bemfuza, udibanise kwi-vitro kwiithagethi ezithile zethumba elikhuluisixhobo sokulwa nabasebenzi "i-chimeric antigen receptor (CAR)", kwaye emva koko ifake iiseli ze-T ezitshintshileyoukubuyela kumzimba wesigulana, i-receptors entsha ehlaziyiweyo iya kufana nokufaka inkqubo ye-radar,ekwaziyo ukukhokela iiseli ze-T zifumane kwaye zitshabalalise iiseli zomhlaza.
Inzuzo ye-CART kwi-BPIH
Ngenxa yokungafani kwesakhiwo se-intracellular signal domain, i-CAR iphuhlise ezineizizukulwana.Sisebenzisa iCART yesizukulwana samva nje.
1stisizukulwana: Kwakukho kuphela icandelo le-intracellular signal kunye ne-tumor inhibitionisiphumo saba sibi.
2ndisizukulwana: Kongezwe i-molecule ekhuthazayo kwisiseko sesizukulwana sokuqala, kunye neukukwazi kweeseli T ukubulala amathumba kwaphuculwa.
3rdisizukulwana: Ngokusekelwe kwisizukulwana sesibini seCAR, ukukwazi kweeseli ze-T ukuvimbela i-tumorukwanda kunye nokukhuthaza i-apoptosis kwaphuculwa kakhulu.
4thisizukulwana: Iiseli ze-CAR-T zinokubandakanyeka ekucocweni kwabemi beseli yethumba ngeukwenza kusebenze into ephantsi yoshicilelo lwe-NFAT ukukhuthaza i-interleukin-12 emva kweCARiyaqaphela i-antigen ekujoliswe kuyo.
| Isizukulwana | Ukuvuselela Umba | Uphawu |
| 1st | CD3ζ | Ukusebenza kweseli ye-T ethile, iseli ye-cytotoxic T, kodwa ayikwazanga ukwanda kunye nokuhlala ngaphakathi emzimbeni. |
| 2nd | CD3ζ+CD28/4-1BB/OX40 | Yongeza i-costimulator, uphucule ubutyhefu beeseli, amandla okukhula okulinganiselweyo. |
| 3rd | CD3ζ+CD28/4-1BB/OX40+CD134 /CD137 | Yongeza ii-costimulators ezi-2, uphuculeamandla okwandisa kunye netyhefu. |
| 4th | I-gene yokuzibulala / i-Amored CAR-T (12IL) Hamba i-CAR-T | Dibanisa ijini yokuzibulala, vakalisa i-immune factor kunye namanye amanyathelo achanekileyo olawulo. |
Inkqubo yonyango
I-1) Ukuhlukaniswa kweeseli ezimhlophe zegazi: Iiseli ze-T zesigulana zibekwe zodwa kwigazi le-peripheral.
2) ukusebenza kweeseli ze-T: amaso emagnethi (iiseli ezenziweyo zedendritic) ezigqunywe ngamajoni omzimbaisetyenziselwa ukwenza iiseli ze-T zisebenze.
I-3) Ukutshintshwa: Iiseli ze-T zenziwa ngofuzo ukubonisa i-CAR in vitro.
I-4) Ukwandisa: Iiseli ze-T eziguqulwe ngofuzo zikhuliswa kwi-vitro.
I-5) I-Chemotherapy: Isigulane siphathwa kwangaphambili nge-chemotherapy phambi kwe-T cell reinfusion.
I-6) Ukubuyisela kwakhona: Iiseli ze-T eziguqulwe ngokwemfuza zibuyisela umva kwisigulane.
Iimpawu
Iimpawu zeCAR-T
Inkqubo yokuphefumla: Umhlaza wemiphunga (I-cell carcinoma encinci, i-squamous cell carcinoma,i-adenocarcinoma), umhlaza we-nasopharynx, njl.
Inkqubo yokugaya: isibindi, isisu kunye nomhlaza wesisu, njl.
Inkqubo ye-Urinary: Izintso kunye ne-adrenal carcinoma kunye ne-metastatic cnacer, njl.
Inkqubo yegazi: I-Acute and chronic lymphoblastic leukemia (T lymphomangaphandle) njl.
Omnye umhlaza: I-Malignant melanoma, ibele, i-prostae kunye nomhlaza wolwimi, njl.
Utyando lokususa isilonda sokuqala, kodwa ukugonyeka kuphantsi, kwaye ukuchacha kuyacotha.
Amathumba ane-metastasis exhaphakileyo engakwazanga ukuqhubeka notyando.
Impembelelo esecaleni yechemotherapy kunye neradiotherapy inkulu okanye ayivani nechemotherapy kunye neradiotherapy.
Thintela ukuphindaphinda kwethumba emva kotyando, ichemotherapy kunye neradiotherapy.
Iingenelo
I-1) Iiseli ze-CAR T zijoliswe kakhulu kwaye zinokubulala iiseli ze-tumor kunye ne-antigen ekhethekileyo ngokufanelekileyo.
2) Unyango lweeseli ze-CAR-T ludinga ixesha elincinci.I-CAR T idinga elona xesha lifutshane lexesha kwiiseli T zenkcubeko kuba ifuna iiseli ezimbalwa phantsi kwesiphumo sonyango olufanayo.Umjikelo wenkcubeko ye-vitro unokufinyezwa kwiiveki ezi-2, eziye zanciphisa kakhulu ixesha lokulinda.
I-3) I-CAR ayinakuqaphela kuphela i-peptide antigens, kodwa kunye neswekile kunye ne-lipid antigens, ukwandisa uluhlu olujoliswe kuyo lwe-tumor antigens.Unyango lwe-CAR T alukhawulelwanga yi-protein antigens yeeseli zethumba.I-CAR T inokusebenzisa iswekile kunye ne-lipid non-protein antigens yeeseli zethumba ukuchonga ii-antigens kwimilinganiselo emininzi.
4) I-CAR-T inobubanzi obuthile - ukuveliswa kwakhona kwe-spectrum.Ekubeni iisayithi ezithile zibonakaliswa kwiiseli ezininzi ze-tumor, ezifana ne-EGFR, i-CAR gene yale antigen ingasetyenziswa ngokubanzi xa sele yakhiwe.
I-5) Iiseli ze-CAR T zinememori ye-immune kwaye zingaphila emzimbeni ixesha elide.Kubaluleke kakhulu kwezonyango ukuthintela ukuvela kwethumba.