Kodi CAR-T (Chimeric Antigen Receptor T-cell) ndi chiyani?
Choyamba, tiyeni tione momwe chitetezo cha mthupi cha munthu chimagwirira ntchito.
Chitetezo cha mthupi chimapangidwa ndi netiweki ya maselo, minofu, ndi ziwalo zomwe zimagwirira ntchito limodzi kutikuteteza thupi. Limodzi mwa maselo ofunikira omwe amakhudzidwa ndi maselo oyera a magazi, omwe amatchedwanso ma leukocyte,zomwe zimabwera m'mitundu iwiri yofunikira yomwe imaphatikizana kuti ifufuze ndikuwononga tizilombo toyambitsa matenda kapenazinthu.
Mitundu iwiri yofunikira ya leukocytes ndi:
Ma phagocyte, omwe amatafuna zamoyo zomwe zimalowa m'thupi.
Lymphocytes, maselo omwe amalola thupi kukumbukira ndi kuzindikira omwe adalowa kale ndikuthandizirathupi liwawononge.
Maselo osiyanasiyana amaonedwa kuti ndi ma phagocyte. Mtundu wofala kwambiri ndi ma neutrophil,zomwe zimalimbana kwambiri ndi mabakiteriya. Ngati madokotala akuda nkhawa ndi matenda a bakiteriya, angapemphekuyezetsa magazi kuti muwone ngati wodwala ali ndi kuchuluka kwa ma neutrophils omwe ayambitsidwa ndi kachilomboka.
Mitundu ina ya ma phagocyte ili ndi ntchito yawoyawo yowonetsetsa kuti thupi limayankha moyenerakwa mtundu winawake wa woukira.
Mitundu iwiri ya ma lymphocyte ndi ma B lymphocyte ndi ma T lymphocyte. Ma Lymphocyte amayambam'mafupa ndipo amakhala pamenepo n'kukhwima kukhala maselo a B, kapena amachoka kupita ku thymusgland, komwe amakula kukhala maselo a T. Ma lymphocyte a B ndi ma lymphocyte a T ali ndi ma lymphocyte osiyanantchito zake: Ma B lymphocytes ali ngati dongosolo la nzeru za asilikali a m'thupi, kufunafunaMa T cell ali ngati asilikali, akuwononga zolinga zawooukira omwe dongosolo lanzeru lawazindikira.
Ukadaulo wa maselo a T a Chimeric antigen receptor (CAR): ndi mtundu wa selo lolandiriraChithandizo cha immunotherapy (ACI). Maselo a T a wodwala amafalitsa CAR kudzera mu kukonzanso majiniukadaulo, womwe umapangitsa maselo a T omwe amagwira ntchito kukhala ofunikira kwambiri, oopsa komanso opitilirapo kuposamaselo ochiritsira chitetezo chamthupi, ndipo amatha kugonjetsa chilengedwe cha m'deralo choletsa chitetezo chamthupi chaKulimbana ndi matenda a khansa ndi kusweka kwa chitetezo cha mthupi. Iyi ndi njira yapadera yolimbana ndi khansa ya m'thupi.
Mfundo ya CART ndikuchotsa "mtundu wamba" wa maselo a T a chitetezo chamthupi cha wodwalayo.ndikupitiriza kupanga majini, kusonkhanitsa mu vitro kuti mupeze zolinga zenizeni za chotupa cha matenda akuluakuluchida chotsutsana ndi antchito "chimeric antigen receptor (CAR)", kenako chimalowetsa maselo a T osinthidwaKubwerera m'thupi la wodwalayo, ma receptors atsopano osinthidwa adzakhala ngati kukhazikitsa radar system,yomwe imatha kutsogolera maselo a T kupeza ndikuwononga maselo a khansa.
Ubwino wa CART ku BPIH
Chifukwa cha kusiyana kwa kapangidwe ka chizindikiro cha mkati mwa maselo, CAR yapanga zinayimibadwo. Timagwiritsa ntchito CART ya mibadwo yatsopano.
1stm'badwo: Panali gawo limodzi lokha la chizindikiro cha mkati mwa maselo ndi choletsa chotupazotsatira zake zinali zoipa.
2ndm'badwo: Anawonjezera molekyulu yolimbikitsa pamodzi pamaziko a m'badwo woyamba, ndipoMphamvu ya maselo a T kupha zotupa inakula.
3rdm'badwo: Kutengera m'badwo wachiwiri wa CAR, mphamvu ya maselo a T yoletsa chotupaKuchulukana ndi kulimbikitsa apoptosis kunakula kwambiri.
4thkupanga: Maselo a CAR-T akhoza kutenga nawo mbali pakuchotsa maselo a chotupa mwakuyambitsa NFAT yomwe imayambitsa interleukin-12 pambuyo pa CARimazindikira antigen yomwe ikufunidwa.
| Mbadwo | Kulimbikitsa Factor | Mbali |
| 1st | CD3ζ | Kuyambitsa maselo a T enieni, maselo a T omwe ali ndi poizoni, koma sanathe kuchulukana ndi kupulumuka mkati mwa thupi. |
| 2nd | CD3ζ+CD28/4-1BB/OX40 | Onjezani costimulator, onjezerani poizoni wa maselo, mphamvu yochepa yobereka. |
| 3rd | CD3ζ+CD28/4-1BB/OX40+CD134/CD137 | Onjezani ma costimulators awiri, sinthanimphamvu yoberekana ndi poizoni. |
| 4th | Jini lodzipha/CAR-T yotetezedwa (12IL) Pitani ku CAR-T | Phatikizani majini odzipha, mphamvu yodziteteza ku matenda ndi njira zina zowongolera molondola. |
Njira yothandizira
1) Kupatula maselo oyera m'magazi: Maselo a T a wodwala amachotsedwa m'magazi a m'mbali.
2) Kuyambitsa kwa maselo a T: mikanda ya maginito (maselo a dendritic opangidwa) okhala ndi ma antibodies ndiamagwiritsidwa ntchito kuyambitsa maselo a T.
3) Kutumiza kachilombo: Maselo a T amapangidwa kuti azitha kutulutsa CAR m'thupi.
4) Kukulitsa: Maselo a T osinthidwa majini amakulitsidwa mu vitro.
5) Chemotherapy: Wodwalayo amalandira chithandizo cha chemotherapy asanalowetsedwenso maselo a T.
6) Kubwezeretsanso: Maselo a T osinthidwa majini amabwereranso mwa wodwalayo.
Zizindikiro
Zizindikiro za CAR-T
Matenda a kupuma: Khansa ya m'mapapo (Khansa yaing'ono ya maselo, khansa ya squamous cell,adenocarcinoma), khansa ya nasopharynx, ndi zina zotero.
Matenda a m'mimba: khansa ya chiwindi, m'mimba ndi m'matumbo, ndi zina zotero.
Dongosolo la mkodzo: Impso ndi khansa ya adrenal ndi khansa ya metastatic, ndi zina zotero.
Magazi: Matenda a khansa ya m'magazi (T lymphoma) komanso matenda aakulu a lymphoblastic leukemia (Acute and chronic lymphoma).osachotsedwa) ndi zina zotero.
Khansa ina: Khansa yoopsa ya melanoma, khansa ya m'mawere, khansa ya prostate ndi lilime, ndi zina zotero.
Opaleshoni yochotsa chilonda choyamba, koma chitetezo chamthupi chimakhala chochepa, ndipo chithandizocho chimachedwa.
Zotupa zomwe zili ndi kufalikira kwa khansa zomwe sizingathe kupitiliza ndi opaleshoni.
Zotsatira zoyipa za chemotherapy ndi radiotherapy zimakhala zazikulu kapena sizimakhudzidwa ndi chemotherapy ndi radiotherapy.
Pewani kubwereranso kwa chotupa pambuyo pa opaleshoni, chemotherapy ndi radiotherapy.
Ubwino
1) Maselo a CAR T ndi omwe amakhudzidwa kwambiri ndipo amatha kupha maselo a chotupa omwe ali ndi antigen yeniyeni bwino.
2) Chithandizo cha maselo a CAR-T chimafuna nthawi yochepa. CAR T imafuna nthawi yochepa kwambiri yopangira maselo a T chifukwa imafuna maselo ochepa omwe ali ndi zotsatira zofanana za chithandizo. Nthawi yopangira maselo m'thupi imatha kuchepetsedwa kufika pa masabata awiri, zomwe zimachepetsa kwambiri nthawi yodikira.
3) CAR imatha kuzindikira osati ma peptide antigen okha, komanso ma lipid antigen a shuga ndi lipid, kukulitsa kuchuluka kwa ma antibodies a chotupa. Chithandizo cha CAR T sichimachepetsedwanso ndi ma protein antigen a maselo a chotupa. CAR T ingagwiritse ntchito ma protein antigen a shuga ndi lipid omwe si mapuloteni a maselo a chotupa kuti izindikire ma antibodies m'njira zosiyanasiyana.
4) CAR-T ili ndi kuthekera koberekanso kwapadera. Popeza malo ena amapezeka m'maselo ambiri a chotupa, monga EGFR, jini ya CAR ya antigen iyi ingagwiritsidwe ntchito kwambiri ikapangidwa.
5) Maselo a CAR T ali ndi ntchito yokumbukira chitetezo chamthupi ndipo amatha kukhalabe m'thupi kwa nthawi yayitali. Ndikofunikira kwambiri kuchipatala kuti tipewe kubwereranso kwa chotupa.