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 kunye ukukhusela umzimba.Enye yeeseli ezibalulekileyo ezibandakanyekayo ziiseli ezimhlophe zegazi, ezikwabizwa ngokuba yi-leukocytes, eziza kwiindidi ezimbini ezisisiseko ezidibanisa ukukhangela nokutshabalalisa izinto eziphilayo ezibangela izifo okanye izinto.
Iintlobo ezimbini ezisisiseko ze-leukocytes zezi:
Ø i-phagocytes, iiseli ezihlafuna izinto eziphilayo ezihlaselayo
Ø i-lymphocytes, iiseli ezivumela umzimba ukuba ukhumbule kwaye uqaphele abahlaseli bangaphambili kwaye uncede umzimba ubatshabalalise
Inani leeseli ezahlukeneyo zithathwa njenge-phagocytes.Olona hlobo luxhaphakileyo yineutrophil, elwa ikakhulu neebhaktheriya.Ukuba oogqirha banexhala malunga nosulelo lwebhaktheriya, banokuyalela uvavanyo lwegazi ukubona ukuba isigulana sinenani elongeziweyo lee-neutrophils ezibangelwa lusulelo.Ezinye iintlobo ze-phagocytes zinemisebenzi yazo yokuqinisekisa ukuba umzimba uphendula ngokufanelekileyo kuhlobo oluthile lomhlaseli.
Ezi ntlobo zimbini ze-lymphocytes yi-B lymphocytes kunye ne-T lymphocytes.I-lymphocyte iqala kumongo wethambo kwaye ihlale apho kwaye ikhule ibe ziiseli ze-B, okanye ihambe iye kwi-thymus gland, apho ikhulela kwiiseli ze-T.I-B lymphocytes kunye ne-T lymphocytes zinemisebenzi eyahlukileyo: Ii-lymphocyte ze-B zifana nenkqubo yengqondo yezempi yomzimba, ifuna iithagethi zazo kwaye ithumela izixhobo zokukhusela ukuba zitshixe kuzo.Ii-T cells zifana namajoni, zitshabalalisa abahlaseli abachongwe yinkqubo yezobuntlola.
Ukhuselo lomzimba lwenziwe luthungelwano lweeseli, izicubu, kunye namalungu asebenza kunye ukukhusela umzimba.Enye yeeseli ezibalulekileyo ezibandakanyekayo ziiseli ezimhlophe zegazi, ezikwabizwa ngokuba yi-leukocytes, eziza kwiindidi ezimbini ezisisiseko ezidibanisa ukukhangela nokutshabalalisa izinto eziphilayo ezibangela izifo okanye izinto.
Iintlobo ezimbini ezisisiseko ze-leukocytes zezi:
Ø i-phagocytes, iiseli ezihlafuna izinto eziphilayo ezihlaselayo
Ø i-lymphocytes, iiseli ezivumela umzimba ukuba ukhumbule kwaye uqaphele abahlaseli bangaphambili kwaye uncede umzimba ubatshabalalise
Inani leeseli ezahlukeneyo zithathwa njenge-phagocytes.Olona hlobo luxhaphakileyo yineutrophil, elwa ikakhulu neebhaktheriya.Ukuba oogqirha banexhala malunga nosulelo lwebhaktheriya, banokuyalela uvavanyo lwegazi ukubona ukuba isigulana sinenani elongeziweyo lee-neutrophils ezibangelwa lusulelo.Ezinye iintlobo ze-phagocytes zinemisebenzi yazo yokuqinisekisa ukuba umzimba uphendula ngokufanelekileyo kuhlobo oluthile lomhlaseli.
Ezi ntlobo zimbini ze-lymphocytes yi-B lymphocytes kunye ne-T lymphocytes.I-lymphocyte iqala kumongo wethambo kwaye ihlale apho kwaye ikhule ibe ziiseli ze-B, okanye ihambe iye kwi-thymus gland, apho ikhulela kwiiseli ze-T.I-B lymphocytes kunye ne-T lymphocytes zinemisebenzi eyahlukileyo: Ii-lymphocyte ze-B zifana nenkqubo yengqondo yezempi yomzimba, ifuna iithagethi zazo kwaye ithumela izixhobo zokukhusela ukuba zitshixe kuzo.Ii-T cells zifana namajoni, zitshabalalisa abahlaseli abachongwe yinkqubo yezobuntlola.
I-Chimeric antigen receptor (CAR) itekhnoloji yeseli ye-T: luhlobo lwe-adoptive cell immunotherapy (ACI).Iseli ye-T yesigulana ivakalisa i-CAR ngokusebenzisa itekhnoloji yokwakhiwa ngokutsha kwemfuza, eyenza iiseli ze-T zijolise ngakumbi, zibulale kwaye zizingise kuneeseli zokhuselo lomzimba, kwaye zinokoyisa i-immune immunosuppressive microenvironment ye-tumor kunye nokwaphula ukunyamezelana komzimba.Olu lunyango oluthile lwe-immune cell anti - tumor.
Umgaqo we-CART kukuthatha "uguqulelo oluqhelekileyo" lweeseli ze-T zomzimba zesigulana kwaye uqhubeke nobunjineli bejini, ukuqokelela kwi-vitro kwiithagethi ezithile zethumba lesixhobo esikhulu sokulwa nabasebenzi "i-chimeric antigen receptor (CAR)", kwaye emva koko ifake utshintsho. Iiseli ze-T zibuyela kumzimba wesigulane, ii-receptors zeseli ezitshintshiweyo ziya kufana nokufaka inkqubo ye-radar, ekwazi ukukhokela iiseli ze-T zifumane kwaye zitshabalalise iiseli zomhlaza.
Inzuzo ye-CART kwi-BPIH
Ngenxa yokungafani kwesakhiwo se-intracellular signal domain, i-CAR iphuhlise izizukulwana ezine.Sisebenzisa iCART yesizukulwana samva nje.
1Stisizukulwana: Kwakukho kuphela icandelo le-intracellular signal kunye ne-tumor inhibition effect yayingalunganga.
2ndisizukulwana: Kongezwa i-molecule ekhuthazayo kwisiseko sesizukulwana sokuqala, kunye nokukwazi kweeseli ze-T ukubulala amathumba kwaphuculwa.
3rdisizukulwana: Ngokusekelwe kwisizukulwana sesibini se-CAR, ukukwazi kweeseli ze-T ukuvimbela ukwanda kwe-tumor kunye nokukhuthaza i-apoptosis kwaphuculwa kakhulu.
4thisizukulwana: Iiseli ze-CAR-T zinokubandakanyeka ekucocweni kwe-tumor cell population ngokuvula i-downstream transcription factor NFAT ukuze ifake i-interleukin-12 emva kokuba i-CAR ibone i-antigen ekujoliswe kuyo.
Inkqubo yonyango
I-1) Ukuhlukaniswa kweeseli ezimhlophe zegazi: Iiseli ze-T zesigulana zibekwe zodwa kwigazi le-peripheral;
I-2) ukusebenza kweeseli ze-T: amaso amagnetic (iiseli ze-dendritic ezenziweyo) ezifakwe kwi-antibodies zisetyenziselwa ukwenza iiseli ze-T zisebenze;
Ukudluliselwa: Iiseli ze-T zenziwe ngofuzo ukubonisa i-CAR kwi-vitro.
I-3) Ukwandisa: Iiseli ze-T eziguqulwe ngofuzo zikhuliswa kwi-vitro.
I-4) I-Chemotherapy: Isigulane siphathwa kwangaphambili nge-chemotherapy phambi kwe-T cell reinfusion;
I-5) Ukubuyisela kwakhona: Iiseli ze-T eziguqulwe ngokwemfuza zibuyisela umva kwisigulane.
Izinto eziluncedo:
1)Iiseli ze-CAR T zijoliswe kakhulu kwaye zinokubulala iiseli zethumba kunye ne-antigen ekhethekileyo ngokufanelekileyo.
2)Unyango lweeseli ze-CAR-T lufuna 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.
3)I-CAR ayinakuqaphela kuphela ii-antigens ze-peptide, 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.
5)Iiseli zeCAR T zinomsebenzi wokukhumbula i-immune kwaye zinokuphila emzimbeni ixesha elide.Kubaluleke kakhulu kwezonyango ukuthintela ukuvela kwethumba.