Kodi CAR-T (Chimeric Antigen Receptor T-cell) ndi chiyani?
Choyamba, tiyeni tione mmene chitetezo cha mthupi cha munthu chimakhalira.
Chitetezo cha mthupi chimapangidwa ndi ma cell, minofu, ndi ziwalo zomwe zimagwirira ntchito limodzi kuteteza thupi.Mmodzi mwa maselo ofunikira omwe amakhudzidwa ndi maselo oyera a magazi, omwe amatchedwanso leukocytes, omwe amabwera m'magulu awiri omwe amaphatikizana kuti afufuze ndi kuwononga tizilombo toyambitsa matenda.
Mitundu iwiri yayikulu ya leukocyte ndi:
Ø phagocytes, maselo omwe amatafuna zamoyo zomwe zikubwera
Ø ma lymphocyte, maselo omwe amalola kuti thupi likumbukire ndikuzindikira omwe adalowa kale ndikuthandizira thupi kuwawononga
Maselo angapo osiyanasiyana amatengedwa ngati phagocytes.Mtundu wodziwika kwambiri ndi neutrophil, womwe umalimbana ndi mabakiteriya.Ngati madokotala akuda nkhawa ndi matenda a bakiteriya, amatha kuyitanitsa kuyezetsa magazi kuti awone ngati wodwala ali ndi kuchuluka kwa ma neutrophils omwe amayamba chifukwa cha matendawa.Mitundu ina ya phagocyte ili ndi ntchito zawo kuti zitsimikizire kuti thupi limayankha moyenera ku mtundu wina wa wowukira.
Mitundu iwiri ya ma lymphocyte ndi B lymphocytes ndi T lymphocytes.Ma lymphocyte amayambira m'mafupa ndipo amakhala pamenepo ndikukula kukhala ma cell B, kapena amapita ku thymus gland, komwe amakhwima kukhala ma T cell.Ma lymphocyte a B ndi T lymphocyte ali ndi ntchito zosiyana: Ma lymphocyte a B ali ngati gulu lankhondo lankhondo, kufunafuna zomwe akufuna ndikutumiza zoteteza kuti zitseke.Maselo a T ali ngati asilikali, akuwononga adani omwe gulu lanzeru lazindikira.
Chitetezo cha mthupi chimapangidwa ndi ma cell, minofu, ndi ziwalo zomwe zimagwirira ntchito limodzi kuteteza thupi.Mmodzi mwa maselo ofunikira omwe amakhudzidwa ndi maselo oyera a magazi, omwe amatchedwanso leukocytes, omwe amabwera m'magulu awiri omwe amaphatikizana kuti afufuze ndi kuwononga tizilombo toyambitsa matenda.
Mitundu iwiri yayikulu ya leukocyte ndi:
Ø phagocytes, maselo omwe amatafuna zamoyo zomwe zikubwera
Ø ma lymphocyte, maselo omwe amalola kuti thupi likumbukire ndikuzindikira omwe adalowa kale ndikuthandizira thupi kuwawononga
Maselo angapo osiyanasiyana amatengedwa ngati phagocytes.Mtundu wodziwika kwambiri ndi neutrophil, womwe umalimbana ndi mabakiteriya.Ngati madokotala akuda nkhawa ndi matenda a bakiteriya, amatha kuyitanitsa kuyezetsa magazi kuti awone ngati wodwala ali ndi kuchuluka kwa ma neutrophils omwe amayamba chifukwa cha matendawa.Mitundu ina ya phagocyte ili ndi ntchito zawo kuti zitsimikizire kuti thupi limayankha moyenera ku mtundu wina wa wowukira.
Mitundu iwiri ya ma lymphocyte ndi B lymphocytes ndi T lymphocytes.Ma lymphocyte amayambira m'mafupa ndipo amakhala pamenepo ndikukula kukhala ma cell B, kapena amapita ku thymus gland, komwe amakhwima kukhala ma T cell.Ma lymphocyte a B ndi T lymphocyte ali ndi ntchito zosiyana: Ma lymphocyte a B ali ngati gulu lankhondo lankhondo, kufunafuna zomwe akufuna ndikutumiza zoteteza kuti zitseke.Maselo a T ali ngati asilikali, akuwononga adani omwe gulu lanzeru lazindikira.
Chimeric antigen receptor(CAR) T cell technology: ndi mtundu wa adoptive cellular immunotherapy(ACI).Odwala T cell kufotokoza CAR kudzera chibadwa kumangidwanso luso, amene effector T maselo kwambiri chandamale, akupha ndi kulimbikira kuposa maselo ochiritsira chitetezo, ndipo akhoza kugonjetsa m`deralo immunosuppressive microenvironment chotupa ndi kuswa khamu chitetezo kulolerana.Ichi ndi mankhwala enieni a chitetezo chamthupi odana ndi chotupa.
Mfundo ya CART ndikuchotsa "mawonekedwe anthawi zonse" a maselo a chitetezo chamthupi a wodwalayo ndikupitilira uinjiniya wa majini, kusonkhanitsa mu vitro kuti apeze zotupa za chida chachikulu cha antipersonnel "chimeric antigen receptor (CAR)", kenako ndikulowetsa zomwe zasinthidwa. Ma cell a T kubwerera m'thupi la wodwalayo, zolandilira zatsopano zosinthidwa zimakhala ngati kukhazikitsa radar system, yomwe imatha kutsogolera ma cell a T kupeza ndikuwononga maselo a khansa.
Ubwino wa CART ku BPIH
Chifukwa cha kusiyana kwa kapangidwe ka intracellular sign domain, CAR yapanga mibadwo inayi.Timagwiritsa ntchito CART yaposachedwa.
1stm'badwo: Panali gawo limodzi lokha la chizindikiro cha intracellular ndipo chotupa choletsa chotupa chinali choyipa.
2ndm'badwo: Anawonjezera co-stimulating molekyulu pa maziko a m'badwo woyamba, ndi mphamvu ya T maselo kupha zotupa anali bwino.
3rdm'badwo: Kutengera m'badwo wachiwiri wa CAR, kuthekera kwa maselo a T kuletsa kuchuluka kwa chotupa ndikulimbikitsa apoptosis kunasintha kwambiri.
4thm'badwo: Ma cell a CAR-T amatha kutenga nawo gawo pakuchotsa kuchuluka kwa maselo otupa poyambitsa cholembera chapansi cha NFAT kuti chipangitse interleukin-12 CAR itazindikira antigen yomwe ikufuna.
Njira yothandizira
1) Kudzipatula kwa maselo oyera a magazi: Maselo a T a wodwala amakhala olekanitsidwa ndi magazi ozungulira;
2) T ma cell activation: maginito mikanda (yopanga dendritic maselo) yokutidwa ndi ma antibodies ntchito yambitsa T maselo;
Kusintha: Ma cell a T amapangidwa mwachibadwa kuti afotokoze CAR mu vitro.
3) Kukulitsa: Maselo a T osinthidwa ndi ma genetic amakulitsidwa mu vitro.
4) Chemotherapy: Wodwalayo amachiritsidwa kale ndi chemotherapy pamaso pa T cell reinfusion;
5) Kulowetsedwanso: Maselo a T osinthidwa mwachibadwa amalowetsa mmbuyo mwa wodwalayo.
Ubwino:
1)Ma cell a CAR T amakhala olunjika kwambiri ndipo amatha kupha maselo otupa omwe ali ndi antigen mwachindunji.
2)CAR-T cell therapy imafuna nthawi yochepa.CAR T imafuna nthawi yaifupi kwambiri ku maselo a T a chikhalidwe chifukwa imafuna maselo ochepa omwe ali pansi pa chithandizo chomwecho.Kuzungulira kwa chikhalidwe cha vitro kumatha kufupikitsidwa mpaka masabata a 2, zomwe zidachepetsa nthawi yodikirira.
3)CAR imatha kuzindikira osati ma antigen a peptide, komanso shuga ndi lipid antigen, kukulitsa chandamale cha ma antigen a chotupa.Chithandizo cha CAR T sichimangokhala ndi ma antigen a protein a cell chotupa.CAR T ikhoza kugwiritsa ntchito ma antigen a shuga ndi lipid omwe sali mapuloteni a maselo otupa kuti azindikire ma antigen osiyanasiyana.
4)CAR-T ili ndi kufalikira kwina kwa sipekitiramu.Popeza malo ena amawonetsedwa m'maselo angapo otupa, monga EGFR, jini ya CAR ya antigen iyi ingagwiritsidwe ntchito kwambiri ikangomangidwa.
5)Ma cell a CAR T ali ndi chitetezo chamthupi chokumbukira ntchito ndipo amatha kukhalabe m'thupi kwa nthawi yayitali.Ndikofunikira kwambiri kuchipatala kuti chotupa chisabwerenso.