Menene CAR-T (Cell T-receptor na Chimeric Antigen Receptor)?
Da farko, bari mu dubi tsarin garkuwar jikin dan adam.
Tsarin garkuwar jiki ya ƙunshi hanyar sadarwa ta ƙwayoyin halitta, kyallen takarda, da gabobin jiki waɗanda ke aiki tare donKare jiki. Ɗaya daga cikin muhimman ƙwayoyin halitta da abin ya shafa sune ƙwayoyin jinin fari, waɗanda kuma ake kira leukocytes,waɗanda suka zo cikin nau'i biyu na asali waɗanda suka haɗu don neman da kuma lalata ƙwayoyin cuta masu haifar da cututtuka koabubuwa.
Babban nau'ikan leukocytes guda biyu sune:
Phagocytes, ƙwayoyin halitta waɗanda ke tauna ƙwayoyin cuta masu mamaye jiki.
Lymphocytes, ƙwayoyin halitta waɗanda ke ba jiki damar tunawa da gane mahara da suka gabata da kuma taimakawajiki yana lalata su.
Ana ɗaukar wasu ƙwayoyin halitta daban-daban a matsayin phagocytes. Nau'in da ya fi yawa shine neutrophil,wanda galibi yake yaƙi da ƙwayoyin cuta. Idan likitoci suna damuwa game da kamuwa da ƙwayoyin cuta, suna iya yin odar maganigwajin jini don ganin ko majiyyaci yana da ƙaruwar adadin neutrophils da kamuwa da cuta ta haifar.
Sauran nau'ikan phagocytes suna da nasu ayyukan don tabbatar da cewa jiki yana amsawa yadda ya kamataga wani takamaiman nau'in mamaya.
Nau'ikan lymphocytes guda biyu sune B lymphocytes da T lymphocytes. Lymphocytes suna farawaa cikin bargo na ƙashi kuma ko dai su zauna a can su girma zuwa ƙwayoyin B, ko kuma su bar ga thymusgland, inda suke girma zuwa ƙwayoyin T. Limfotika B da Limfotika T suna da nau'ikan daban-dabanayyuka: B lymphocytes suna kama da tsarin leƙen asiri na soja na jiki, suna neman susuna kai hari da aika kariya don kulle su. Kwayoyin T suna kama da sojoji, suna lalata sumasu mamaye da tsarin leƙen asiri ya gano.
Fasahar ƙwayoyin T ta Chimeric antigen receptor (CAR): wani nau'in ƙwayar halitta ce da ake ɗauka a matsayin mai karɓar ƙwayoyin halittaMaganin rigakafi (ACI). Ƙwayoyin T na majiyyaci suna bayyana CAR ta hanyar sake gina kwayoyin halittafasahar zamani, wadda ke sa ƙwayoyin T masu tasiri su fi kai hari, su mutu kuma su daɗe fiye daƙwayoyin rigakafi na gargajiya, kuma suna iya shawo kan yanayin hana garkuwar jiki na gidajuriya ga ciwon daji da kuma karyewar garkuwar jiki. Wannan magani ne na musamman na ƙwayoyin rigakafi na hana ciwon daji.
Ka'idar CART ita ce a cire "nau'in da aka saba" na ƙwayoyin T na garkuwar jiki na majiyyaci.da kuma ci gaba da aikin injiniyan kwayoyin halitta, a haɗa su a cikin vitro don takamaiman abubuwan da ke haifar da ciwon dajimakamin antipersonnel "chimeric antigen receptor (CAR)", sannan a saka ƙwayoyin T da aka canza a cikin ƙwayoyin Tidan aka koma jikin majiyyaci, sabbin masu karɓar ƙwayoyin halitta da aka gyara za su yi kama da shigar da tsarin radar,wanda ke iya jagorantar ƙwayoyin T don gano da kuma lalata ƙwayoyin cutar kansa.
Amfanin CART a BPIH
Saboda bambance-bambancen da ke cikin tsarin yankin siginar ƙwayoyin halitta, CAR ta haɓaka huɗutsararraki. Muna amfani da sabuwar tsarar CART.
1sttsarawa: Akwai siginar sigina guda ɗaya kawai da kuma hana ciwace-ciwacentasirin bai yi kyau ba.
2ndtsara: An ƙara wani ƙwayar haɗin gwiwa bisa ga ƙarni na farko, kumaAn inganta ikon ƙwayoyin T na kashe ƙari.
3rdtsarawa: Dangane da ƙarni na biyu na CAR, ikon ƙwayoyin T don hana ciwon dajiAn inganta yaduwar cutar da kuma haɓaka apoptosis sosai.
4thTsarin halitta: Kwayoyin CAR-T na iya shiga cikin share yawan ƙwayoyin ciwon daji ta hanyarkunna factor transcription factor NFAT don haifar da interleukin-12 bayan CARgane abin da ake nufi da antigen.
| Tsarawa | Ƙarfafawa Ma'auni | Fasali |
| 1st | CD3ζ | Takamaiman kunna ƙwayoyin T, ƙwayoyin T masu guba, amma ba za su iya yaduwa da rayuwa a cikin jiki ba. |
| 2nd | CD3ζ+CD28/4-1BB/OX40 | Ƙara costimulator, inganta gubar ƙwayoyin halitta, iyawar yaduwa mai iyaka. |
| 3rd | CD3ζ+CD28/4-1BB/OX40+CD134 /CD137 | Ƙara costimulators guda biyu, ingantaikon yaduwa da guba. |
| 4th | Kwayar halittar kashe kai/Amored CAR-T (12IL) Go CAR-T | Haɗa kwayar halittar kashe kai, sinadarin garkuwar jiki mai ƙarfi da sauran matakan kulawa daidai. |
Tsarin magani
1) Keɓewar ƙwayoyin jinin fararen fata: Ana ware ƙwayoyin T na majiyyaci daga jinin da ke kewaye.
2) Kunna ƙwayoyin T: ƙwayoyin maganadisu (ƙwayoyin dendritic na wucin gadi) waɗanda aka lulluɓe da ƙwayoyin rigakafi an lulluɓe su da ƙwayoyin rigakafi.ana amfani da shi don kunna ƙwayoyin T.
3) Canja wurin Kwayoyin Halitta: An ƙera ƙwayoyin T don bayyana CAR a cikin vitro.
4) Ƙarfafawa: Ana ƙara ƙwayoyin T da aka gyara ta hanyar halitta a cikin vitro.
5) Maganin Chemotherapy: Ana yi wa majiyyaci magani kafin a sake haɗa ƙwayoyin T.
6) Sake yin amfani da kwayoyin halitta: Kwayoyin T da aka gyara suna sake shiga cikin majiyyaci.
Alamomi
Alamomi ga CAR-T
Tsarin Numfashi: Ciwon huhu (Ƙaramin ciwon daji na ƙwayoyin halitta, ciwon daji na ƙwayoyin halitta,ciwon daji na nasopharynx, da sauransu.
Tsarin narkewar abinci: Ciwon hanta, ciki da hanji, da sauransu.
Tsarin fitsari: Ciwon daji na koda da adrenal da kuma ciwon daji na metastatic, da sauransu.
Tsarin Jini: Ciwon sankarar lymphoblastic mai tsanani da na yau da kullun (T lymphoma)ban da) da sauransu.
Sauran ciwon daji: ciwon daji mai tsanani kamar melanoma, ciwon nono, ciwon daji na prostate da harshe, da sauransu.
Ana yin tiyata don cire babban raunin, amma garkuwar jiki ba ta da ƙarfi, kuma dawowar ba ta da jinkiri.
Ciwon daji da ke da yaduwar ƙwayoyin cuta waɗanda ba za a iya yi musu tiyata ba.
Illolin chemotherapy da radiotherapy suna da yawa ko kuma ba sa shafar chemotherapy da radiotherapy.
Hana sake kamuwa da ciwon daji bayan tiyata, chemotherapy da radiotherapy.
Fa'idodi
1) Kwayoyin CAR T suna da matuƙar tasiri kuma suna iya kashe ƙwayoyin ƙari tare da takamaiman antigen yadda ya kamata.
2) Maganin ƙwayoyin CAR-T yana buƙatar ƙarancin lokaci. CAR T yana buƙatar mafi ƙarancin lokaci don haɓaka ƙwayoyin T saboda yana buƙatar ƙananan ƙwayoyin halitta a ƙarƙashin tasirin magani iri ɗaya. Za a iya rage zagayowar al'adar vitro zuwa makonni 2, wanda hakan ya rage lokacin jira sosai.
3) CAR ba wai kawai tana iya gane antigens na peptide ba, har ma da sukari da lipid antigens, wanda ke faɗaɗa kewayon antigens na ƙari. Maganin CAR T kuma ba ya iyakance ga antigens na furotin na ƙwayoyin ƙari. CAR T na iya amfani da sukari da lipid antigens marasa furotin na ƙwayoyin ƙari don gano antigens a cikin girma daban-daban.
4) CAR-T yana da wani nau'in sake haifuwa mai faɗi. Tunda wasu wurare suna bayyana a cikin ƙwayoyin ƙari da yawa, kamar EGFR, ana iya amfani da kwayar halittar CAR don wannan antigen sosai da zarar an gina ta.
5) Kwayoyin CAR T suna da aikin ƙwaƙwalwar garkuwar jiki kuma suna iya rayuwa a cikin jiki na dogon lokaci. Yana da matuƙar muhimmanci a hana sake dawowar ciwon daji.