Iyini i-CAR-T (i-Chimeric Antigen Receptor T-cell)?
Okokuqala, ake sibheke isimiso somzimba sokuzivikela somzimba womuntu.
Uhlelo lokuzivikela komzimba lwakhiwe inethiwekhi yamaseli, izicubu, kanye nezitho zomzimba ezisebenzisana ukuzeukuvikela umzimba. Elinye lamaseli abalulekile ahilelekile amaseli amhlophe egazi, abizwa nangokuthi ama-leukocyte,eziza ngezinhlobo ezimbili eziyisisekelo ezihlangana ukufuna nokubhubhisa izinto eziphilayo ezibangela izifo nomaizinto.
Izinhlobo ezimbili eziyisisekelo zama-leukocyte yilezi:
Ama-phagocyte, amaseli ahlafuna izinto eziphilayo ezihlaselayo.
Ama-lymphocyte, amangqamuzana avumela umzimba ukuthi ukhumbule futhi uqaphele abahlaseli bangaphambilini futhi usizeumzimba ubabhubhise.
Amaseli amaningana ahlukene abhekwa njengama-phagocyte. Uhlobo oluvame kakhulu yi-neutrophil,okulwa kakhulu namagciwane. Uma odokotela bekhathazekile ngokutheleleka ngamagciwane, bangase baceleukuhlolwa kwegazi ukuze kubonakale ukuthi isiguli sinenani elandayo lama-neutrophil abangelwa ukutheleleka.
Ezinye izinhlobo zama-phagocyte zinemisebenzi yazo ukuqinisekisa ukuthi umzimba uphendula ngendlela efanelekuhlobo oluthile lomhlaseli.
Izinhlobo ezimbili zama-lymphocyte yi-B lymphocytes kanye ne-T lymphocytes. Ama-lymphocyte aqalaemnkantsheni bese zihlala lapho bese zikhula zibe amaseli e-B, noma ziyahamba ziye e-thymusindlala, lapho ikhula khona ibe amaseli e-T. Ama-lymphocyte e-B nama-lymphocyte e-T ahlukeneimisebenzi: Ama-lymphocyte e-B afana nohlelo lobuhlakani bezempi lomzimba, afunaamatshe ahlosiwe futhi athumela izivikelo ukuze ziboshwe kuwo. Amaseli e-T afana namasosha, abhubhisaabahlaseli abatholwe uhlelo lwezobunhloli.
Ubuchwepheshe be-Chimeric antigen receptor (CAR) T cell: uhlobo lweseli elithathwayoukwelashwa nge-immunotherapy (ACI). Iseli le-T lesiguli liveza i-CAR ngokwakhiwa kabusha kwezakhi zofuzoubuchwepheshe, okwenza amaseli e-T asebenzayo abe sengozini kakhulu, abulale futhi aqhubeke njalo kunalawoamangqamuzana omzimba avamile, futhi anganqoba indawo encane yokucindezela amasosha omzimba yendawoUkubekezelelana kwamasosha omzimba okuvikela isimila kanye nokuqhekeka kwamasosha omzimba. Lokhu kuyindlela ethile yokwelapha amasosha omzimba yokulwa nesimila.
Umgomo we-CART ukususa "inguqulo evamile" yamaseli e-T omzimba esiguli.futhi uqhubeke nobunjiniyela bezakhi zofuzo, uhlanganise i-in vitro ukuze uthole izinhloso ezithile zomdlavuza ezinkuluisikhali sokulwa nabasebenzi "i-chimeric antigen receptor (CAR)", bese sifaka amaseli e-T ashintshiweuma isiguli sibuyela emzimbeni waso, ama-receptor amaseli amasha aguquliwe azofana nokufaka uhlelo lwe-radar,ekwazi ukuqondisa amaseli e-T ukuthola nokubhubhisa amaseli omdlavuza.
Inzuzo ye-CART kwa-BPIH
Ngenxa yokwehluka kwesakhiwo sesizinda sesignali sangaphakathi kweseli, i-CAR ithuthukise ezineizizukulwane. Sisebenzisa iNKANTOLO yesizukulwane sakamuva.
1stisizukulwane: Kwakukhona ingxenye eyodwa kuphela yesignali yangaphakathi kweseli kanye nokuvinjelwa kwesimilaumphumela wawumubi.
2ndisizukulwane: Kwengezwe i-molecule evuselelayo ngokusekelwe esizukulwaneni sokuqala, kanyeAmandla amaseli e-T okubulala izimila athuthukisiwe.
3rdisizukulwane: Ngokusekelwe esizukulwaneni sesibili se-CAR, ikhono lamaseli e-T lokuvimbela isimilaukwanda nokukhuthaza i-apoptosis kuthuthukiswe kakhulu.
4thisizukulwane: Amaseli e-CAR-T angabandakanyeka ekususweni kwenani lamaseli esimila ngokusebenzisakusebenze i-NFAT ye-transcription factor engezansi ukuze kukhuthazwe i-interleukin-12 ngemuva kwe-CARibona i-antigen eqondiwe.
| Isizukulwane | Ukukhuthaza Isici | Isici |
| 1st | I-CD3ζ | Ukusebenza kwamaseli e-T athile, iseli le-T elinobuthi, kodwa alikwazanga ukwanda nokusinda emzimbeni. |
| 2nd | I-CD3ζ+CD28/4-1BB/OX40 | Engeza i-costimulator, thuthukisa ubuthi bamaseli, ikhono lokukhula elilinganiselwe. |
| 3rd | I-CD3ζ+CD28/4-1BB/OX40+CD134/CD137 | Engeza ama-costimulators amabili, thuthukisaikhono lokusabalala kanye nobuthi. |
| 4th | I-gene yokuzibulala/i-Amored CAR-T (12IL) Go CAR-T | Hlanganisa i-suicide gene, i-express immune factor kanye nezinye izindlela zokulawula ezinembile. |
Inqubo yokwelapha
1) Ukuhlukaniswa kwamaseli amhlophe egazi: Amaseli e-T esiguli ahlukaniswa egazini elingaphandle.
2) Ukusebenza kwamaseli e-T: ubuhlalu obunamandla (amaseli e-dendritic okwenziwa) ambozwe ngama-antibodies akhonaisetshenziselwa ukwenza amaseli e-T asebenze.
3) Ukudluliselwa Kwegciwane: Amaseli e-T aklanywe ngofuzo ukuze aveze i-CAR ngaphandle kokusebenzisa i-ejenti.
4) Ukukhulisa: Amaseli e-T aguqulwe ngofuzo akhuliswa ku-vitro.
5) Ukwelashwa ngamakhemikhali: Isiguli siphathwa ngamakhemikhali ngaphambi kokufakwa kabusha kwamaseli e-T.
6) Ukufakwa kabusha: Amaseli e-T aguqulwe ngofuzo aphinde angene esigulini.
Izinkomba
Izinkomba ze-CAR-T
Uhlelo lokuphefumula: Umdlavuza wamaphaphu (i-Small cell carcinoma, i-squamous cell carcinoma,i-adenocarcinoma), umdlavuza we-nasopharynx, njll.
Uhlelo lokugaya ukudla: Umdlavuza wesibindi, isisu kanye nomdlavuza we-colorectal, njll.
Uhlelo lomchamo: I-Kidney kanye ne-adrenal carcinoma kanye ne-metastatic cnacer, njll.
Uhlelo lwegazi: I-leukemia ye-lymphoblastic ebukhali nehlala isikhathi eside (i-T lymphoma)okungafakwanga) njll.
Omunye umdlavuza: I-melanoma ebulalayo, umdlavuza webele, i-prostate kanye nolimi, njll.
Ukuhlinzwa ukuze kususwe isilonda esiyinhloko, kodwa amasosha omzimba aphansi, futhi ukwelashwa kuhamba kancane.
Izimila ezisakazeke kabanzi ezingakwazi ukuqhubeka nokuhlinzwa.
Umphumela ongemuhle we-chemotherapy kanye ne-radiotherapy mkhulu noma awuzweli ku-chemotherapy kanye ne-radiotherapy.
Vimbela ukuvuvukala okuphindaphindiwe ngemva kokuhlinzwa, ukwelashwa ngamakhemikhali kanye nokwelashwa ngemisebe.
Izinzuzo
1) Amaseli e-CAR T ahlosiwe kakhulu futhi angabulala amaseli esimila ngokuqondene ne-antigen ngempumelelo enkulu.
2) Ukwelashwa ngamaseli e-CAR-T kudinga isikhathi esincane. I-CAR T idinga isikhathi esifushane kakhulu sokukhulisa amaseli e-T ngoba idinga amaseli ambalwa ngaphansi komphumela ofanayo wokwelashwa. Umjikelezo wokukhuliswa kwe-vitro ungafinyezwa ube amasonto ama-2, okunciphisa kakhulu isikhathi sokulinda.
3) I-CAR ayikwazi ukubona ama-antigen e-peptide kuphela, kodwa futhi nama-antigen kashukela nama-lipid, yandisa ububanzi obuqondiwe bama-antigen esimila. Ukwelashwa kwe-CAR T akukhawulelwe futhi yi-protein antigens yamaseli esimila. I-CAR T ingasebenzisa ama-antigen kashukela nama-lipid angewona amaprotheni amaseli esimila ukuthola ama-antigen ngezindlela eziningi.
4) I-CAR-T inokuphindaphinda okuthile kwe-wide-spectrum. Njengoba izindawo ezithile zivezwa kumaseli amaningi esimila, njenge-EGFR, i-CAR gene yale antigen ingasetshenziswa kabanzi uma isikhiwe.
5) Amaseli e-CAR T anomsebenzi wokukhumbula amasosha omzimba futhi angaphila emzimbeni isikhathi eside. Kubaluleke kakhulu emtholampilo ukuvimbela ukuphindaphinda kwesimila.