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 ma cell, minofu, ndi ziwalo zomwe zimagwira ntchito limodzi kuti ziteteze thupi. Chimodzi mwa maselo ofunikira omwe amakhudzidwa ndi maselo oyera amagazi, omwe amatchedwanso ma leukocyte, omwe amabwera m'mitundu iwiri yofunikira yomwe imaphatikizana kuti ifufuze ndikuwononga zamoyo kapena zinthu zomwe zimayambitsa matenda.
Mitundu iwiri yofunikira ya leukocytes ndi:
Ø ma phagocyte, maselo omwe amatafuna zamoyo zomwe zikulowa
Ø ma lymphocyte, maselo omwe amalola thupi kukumbukira ndi kuzindikira omwe adalowa kale ndikuthandiza thupi kuwawononga
Maselo osiyanasiyana amaonedwa kuti ndi ma phagocyte. Mtundu wofala kwambiri ndi ma neutrophil, omwe makamaka amalimbana ndi mabakiteriya. Ngati madokotala akuda nkhawa ndi matenda a bakiteriya, angapemphe kuti apimidwe magazi kuti aone ngati wodwala ali ndi kuchuluka kwa ma neutrophil omwe amayamba chifukwa cha matendawa. Mitundu ina ya ma phagocyte ili ndi ntchito yawo yowonetsetsa kuti thupi likuyankha moyenera ku mtundu winawake wa kachilomboka.
Mitundu iwiri ya ma lymphocyte ndi ma B lymphocytes ndi ma T lymphocytes. Ma lymphocytes amayamba mu fupa la mafupa ndipo amakhala pamenepo ndikukhwima kukhala maselo a B, kapena amapita ku thymus gland, komwe amakhwima kukhala maselo a T. Ma B lymphocytes ndi ma T lymphocytes ali ndi ntchito zosiyana: Ma B lymphocytes ali ngati dongosolo lankhondo lankhondo, kufunafuna malo awo ndikutumiza chitetezo kuti chiwatsekere. Ma T cell ali ngati asilikali, kuwononga oukira omwe dongosolo lanzeru lawazindikira.
Chitetezo cha mthupi chimapangidwa ndi ma cell, minofu, ndi ziwalo zomwe zimagwira ntchito limodzi kuti ziteteze thupi. Chimodzi mwa maselo ofunikira omwe amakhudzidwa ndi maselo oyera amagazi, omwe amatchedwanso ma leukocyte, omwe amabwera m'mitundu iwiri yofunikira yomwe imaphatikizana kuti ifufuze ndikuwononga zamoyo kapena zinthu zomwe zimayambitsa matenda.
Mitundu iwiri yofunikira ya leukocytes ndi:
Ø ma phagocyte, maselo omwe amatafuna zamoyo zomwe zikulowa
Ø ma lymphocyte, maselo omwe amalola thupi kukumbukira ndi kuzindikira omwe adalowa kale ndikuthandiza thupi kuwawononga
Maselo osiyanasiyana amaonedwa kuti ndi ma phagocyte. Mtundu wofala kwambiri ndi ma neutrophil, omwe makamaka amalimbana ndi mabakiteriya. Ngati madokotala akuda nkhawa ndi matenda a bakiteriya, angapemphe kuti apimidwe magazi kuti aone ngati wodwala ali ndi kuchuluka kwa ma neutrophil omwe amayamba chifukwa cha matendawa. Mitundu ina ya ma phagocyte ili ndi ntchito yawo yowonetsetsa kuti thupi likuyankha moyenera ku mtundu winawake wa kachilomboka.
Mitundu iwiri ya ma lymphocyte ndi ma B lymphocytes ndi ma T lymphocytes. Ma lymphocytes amayamba mu fupa la mafupa ndipo amakhala pamenepo ndikukhwima kukhala maselo a B, kapena amapita ku thymus gland, komwe amakhwima kukhala maselo a T. Ma B lymphocytes ndi ma T lymphocytes ali ndi ntchito zosiyana: Ma B lymphocytes ali ngati dongosolo lankhondo lankhondo, kufunafuna malo awo ndikutumiza chitetezo kuti chiwatsekere. Ma T cell ali ngati asilikali, kuwononga oukira omwe dongosolo lanzeru lawazindikira.
Ukadaulo wa maselo a T a Chimeric antigen receptor (CAR): ndi mtundu wa chithandizo cha immunotherapy cha maselo olandirira (ACI). Maselo a T a wodwala amawonetsa CAR kudzera muukadaulo wokonzanso majini, zomwe zimapangitsa maselo a T omwe amagwira ntchito kukhala olunjika kwambiri, oopsa komanso okhazikika kuposa maselo wamba a chitetezo chamthupi, ndipo amatha kuthana ndi chilengedwe chapafupi choletsa chitetezo chamthupi cha chotupa ndikuphwanya kulekerera kwa chitetezo chamthupi. Uwu ndi mankhwala apadera oletsa khansa a maselo a chitetezo chamthupi.
Mfundo ya CART ndikutenga "mtundu wamba" wa maselo a T a chitetezo cha mthupi a wodwalayo ndikupitiliza kupanga majini, kusonkhanitsa mu vitro kuti akwaniritse zolinga zenizeni za chotupa cha chida chachikulu chotsutsana ndi antchito "chimeric antigen receptor (CAR)", kenako kuyika maselo a T osinthidwa 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 mibadwo inayi. Timagwiritsa ntchito CART yaposachedwa.
1stm'badwo: Panali gawo limodzi lokha la chizindikiro cha mkati mwa maselo ndipo mphamvu yoletsa chotupa inali yoipa.
2ndm'badwo: Anawonjezera molekyulu yolimbikitsa pamodzi pogwiritsa ntchito m'badwo woyamba, ndipo mphamvu ya maselo a T yopha zotupa inakula.
3rdm'badwo: Kutengera m'badwo wachiwiri wa CAR, kuthekera kwa maselo a T kuletsa kuchulukana kwa chotupa ndikulimbikitsa apoptosis kunakula kwambiri.
4thKupanga: Maselo a CAR-T amatha kutenga nawo mbali pakuchotsa kuchuluka kwa maselo a chotupa mwa kuyambitsa NFAT yomwe ili pansi pa transcription factor kuti ipangitse interleukin-12 CAR ikazindikira antigen yomwe ikufunidwa.
Njira yothandizira
1) Kupatula maselo oyera m'magazi: Maselo a T a wodwala amachotsedwa m'magazi a m'mbali;
2) Kuyambitsa maselo a T: mikanda ya maginito (maselo a dendritic opangidwa) okhala ndi ma antibodies amagwiritsidwa ntchito kuyambitsa maselo a T;
Kupereka Matenda: Maselo a T amapangidwa kuti azitha kutulutsa CAR m'thupi.
3) Kukulitsa: Maselo a T osinthidwa majini amakulitsidwa mu vitro.
4) Chemotherapy: Wodwalayo amalandira chithandizo cha chemotherapy asanalowetsedwenso maselo a T;
5) Kubwezeretsanso: Maselo a T osinthidwa majini amabwereranso mwa wodwalayo.
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 kupewa kubwereranso kwa chotupa.