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 limodzikuteteza thupi.Imodzi mwa maselo ofunikira omwe amakhudzidwa ndi maselo oyera a magazi, omwe amatchedwanso leukocytes,zomwe zimabwera m'mitundu iwiri yofunikira yomwe imaphatikizana kufunafuna ndi kuwononga zamoyo zoyambitsa matenda kapenazinthu.
Mitundu iwiri yayikulu ya leukocyte ndi:
Phagocytes, maselo omwe amatafuna zamoyo zomwe zikubwera.
Lymphocytes, maselo omwe amalola thupi kukumbukira ndikuzindikira omwe adalowa kale ndikuthandizirathupi limawawononga.
Maselo angapo osiyanasiyana amatengedwa ngati phagocytes.Mtundu wodziwika kwambiri ndi neutrophil,zomwe zimalimbana kwambiri ndi mabakiteriya.Ngati madokotala akuda nkhawa ndi matenda a bakiteriya, akhoza kuyitanitsakuyezetsa 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 moyenerakwa mtundu wina wa wowukira.
Mitundu iwiri ya ma lymphocyte ndi B lymphocytes ndi T lymphocytes.Ma lymphocyte amayambam'mafupa ndipo mwina amakhala pamenepo ndikukhwima kukhala ma cell a B, kapena amapita ku thymusgland, kumene amakhwima kukhala ma T cell.B lymphocytes ndi T lymphocytes ali osiyanantchito: B ma lymphocyte ali ngati thupi lankhondo nzeru dongosolo, kufunafuna awomipherezero ndi kutumiza chitetezo kuti atseke pa iwo.T maselo ali ngati asilikali, kuwonongaoukira omwe bungwe la intelligence lawazindikira.
Chimeric antigen receptor(CAR) T cell ukadaulo: ndi mtundu wa ma cell otengeraimmunotherapy (ACI).Ma cell a T a odwala amawonetsa CAR kudzera mu kukonzanso ma genetictekinoloje, yomwe imapangitsa kuti maselo a T azitha kuyang'ana kwambiri, owopsa komanso olimbikira kuposaochiritsira chitetezo maselo, ndipo akhoza kugonjetsa m`deralo immunosuppressive microenvironment wachotupa ndi kuswa khamu chitetezo kulolerana.Ichi ndi mankhwala enieni a chitetezo chamthupi odana ndi chotupa.
Mfundo ya CART ndikuchotsa "mtundu wamba" wa maselo a chitetezo chamthupi a wodwalayondi kupitiriza gene engineering, kusonkhanitsa mu vitro kwa chotupa zolinga zazikuluchida cha antipersonnel "chimeric antigen receptor (CAR)", kenako ndikulowetsa maselo a T osinthidwa.kubwerera m'thupi la wodwalayo, zolandilira zatsopano zosinthidwa zimakhala ngati kukhazikitsa radar system,zomwe zimatha kutsogolera ma T cell kupeza ndikuwononga maselo a khansa.
Ubwino wa CART ku BPIH
Chifukwa cha kusiyana kwa kapangidwe ka intracellular sign domain, CAR yapanga zinayimibadwo.Timagwiritsa ntchito CART yaposachedwa.
1stm'badwo: Panali gawo limodzi lokha la chizindikiro cha intracellular ndi cholepheretsa chotupazotsatira zake zinali zoipa.
2ndm'badwo: Anawonjezera co-stimulating molekyulu pa maziko a m'badwo woyamba, ndiKuthekera kwa ma T cell kupha zotupa kunali bwino.
3rdm'badwo: Kutengera m'badwo wachiwiri wa CAR, kuthekera kwa ma T cell kuletsa chotupakuchuluka ndi kulimbikitsa apoptosis anali bwino kwambiri.
4thm'badwo: Ma cell a CAR-T amatha kutenga nawo gawo pakuchotsa kuchuluka kwa maselo otupa ndikuyambitsa cholembera chapansi cha NFAT kuti chipangitse interleukin-12 pambuyo pa CARamazindikira antigen chandamale.
| M'badwo | Kukondoweza Factor | Mbali |
| 1st | CD3ζ | Kutsegula kwapadera kwa T cell, cytotoxic T cell, koma sikunathe kuchulukana ndi kupulumuka mkati mwa thupi. |
| 2nd | CD3ζ+CD28/4-1BB/OX40 | Onjezani costimulator, sinthani kawopsedwe ka ma cell, kuthekera kochulukirachulukira. |
| 3rd | CD3ζ+CD28/4-1BB/OX40+CD134 /CD137 | Onjezani 2 ma costimulators, sinthanikuchuluka luso ndi kawopsedwe. |
| 4th | Jini wodzipha/Amored CAR-T (12IL) Pitani CAR-T | Phatikizani jini yodzipha, fotokozani chitetezo cha mthupi ndi njira zina zowongolera. |
Njira yothandizira
1) Kudzipatula kwa maselo oyera a magazi: Ma cell a T a wodwala amakhala olekanitsidwa ndi magazi ozungulira.
2) T ma cell activation: maginito mikanda (yopanga dendritic maselo) yokutidwa ndi ma antibodies ndiamagwiritsidwa ntchito kuyambitsa ma T cell.
3) Kusintha: Maselo a T amapangidwa mwachibadwa kuti afotokoze CAR mu vitro.
4) Kukulitsa: Maselo a T osinthidwa ma genetic amakulitsidwa mu vitro.
5) Chemotherapy: Wodwalayo amachiritsidwa kale ndi chemotherapy pamaso pa T cell reinfusion.
6) Kulowetsedwanso: Maselo a T osinthidwa mwachibadwa amalowetsa mmbuyo mwa wodwalayo.
Zizindikiro
Zizindikiro za CAR-T
Njira yopuma: Khansara ya m'mapapo (Small cell carcinoma, squamous cell carcinoma,adenocarcinoma), khansa ya nasopharynx, etc.
M'mimba dongosolo: chiwindi, m'mimba ndi colorectal khansa, etc.
Urinary system: Impso ndi adrenal carcinoma ndi metastatic cnacer, etc.
Magazi: Acute and chronic lymphoblastic leukemia (T lymphomakuchotsedwa) etc.
Khansara ina: khansa ya khansa ya khansa, khansa ya m'mawere, prostae ndi lilime, ndi zina zotero.
Opaleshoni yochotsa chotupa choyambirira, koma chitetezo cha mthupi chimakhala chochepa, ndipo kuchira kumachedwa.
Zotupa ndi metastasis ponseponse kuti sanathe kuchitidwa opaleshoni.
Zotsatira za chemotherapy ndi radiotherapy ndizokulirapo kapena zosakhudzidwa ndi chemotherapy ndi radiotherapy.
Pewani chotupa kubwereza pambuyo pa opaleshoni, chemotherapy ndi radiotherapy.
Ubwino wake
1) Ma cell a CAR T amawongolera 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 ikhoza kuzindikira osati ma antigen a peptide, komanso shuga ndi lipid antigens, kukulitsa chandamale cha antigens 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) Maselo a CAR T ali ndi chitetezo cha kukumbukira chitetezo ndipo amatha kukhala ndi moyo m'thupi kwa nthawi yaitali.Ndikofunikira kwambiri kuchipatala kuti chotupa chisabwerenso.