Juun 2022: Sida laga soo xigtay natiijadii ka soo baxday daraasad ay dhawaan daabacday Daawada Stanford Jiirarka, daawaynta kansarka ee ka faa'iidaysata isticmaalka unugyada difaaca ee hidde ahaan wax laga beddelay ee bukaanka si ay u weeraraan unugyada kansarka ayaa ka badbaado badan oo waxtar badan marka lagu beddelo oo laga saaro dawo afka laga qaato.
Daawaynta ugu horreysa, oo hadda loo yaqaan 'CAR-T cell therapy', ayaa muujisay guul la taaban karo oo lagula dagaallamayo kansarrada dhiigga ee kala duwan. Si kastaba ha noqotee, sababtoo ah xaqiiqda ah in bukaanada qaarkood ay leeyihiin falcelin difaac ah unugyada injineernimada ee suurtagalka ah inay dhintaan, daawaynta CAR-T ayaa caadi ahaan loo qoondeeyay isticmaalka kaliya ka dib markii daawaynta kale marka hore la sahamiyo.
Waxa kale oo ay leedahay guul hoose oo lagu daweynayo bukaanada qaba burooyinka adag, sida kuwa laga helo kansarka maskaxda iyo lafaha. Cilmi-baadhayaashu waxay aaminsan yihiin in tani ay sabab u tahay xaqiiqda ah in unugyada CAR-T ay u nugul yihiin inay helaan qadar xad-dhaaf ah oo calaamad ah, taas oo keenta inay noqdaan kuwo daalan ka hor intaanay tirtirin burooyinka adag. Intaa waxaa dheer, marka la barbardhigo kansarka dhiigga, way adag tahay in la aqoonsado bartilmaameedyada molecular ee burooyinka adag. Bartilmaameedyadan molecular waa inay joogaan oo keliya unugyada kansarka ee maaha inay ku jiraan unugyada caadiga ah si ay u noqdaan doorashooyin daaweyn oo waxtar leh.
The researchers at Stanford came up with a modified CAR-T cell therapy that they call SNIP CAR-T. This therapy is activated by taking an oral medication for hepatitis that the Food and Drug Administration has already given the green light for use in humans. (The SNIP CAR-T cells are inactive if the drug is not administered.)
Bukaannada halista ugu jira inay fal-celin xun ku yeeshaan unugyada hidde ahaan wax laga beddelay waxaa ilaaliya hab badbaado leh oo loo yaqaan awoodda isticmaalka daawada si loo beddelo heerka dhaqdhaqaaqa unugyada ka dib marka dib loogu celiyo bukaanka. Cilmi-baadhayaashu waxay sidoo kale ogaadeen in unugyada CAR-T ee la beddelay ay si aad ah uga waxtar badan yihiin la dagaallanka kansarka adag ee jiirka shaybaarka. Waxay u malaynayaan inay taasi tahay xaaladdu sababtoo ah unugyadu waxay la kulmeen nasasho kooban oo soo noqnoqota iyada oo daawada maalinlaha ah lagu dheefshiido jidhka xayawaanka.
Crystal Mackall, MD. Unugyadan CAR-T ee la beddelay ma aha oo kaliya ammaan, laakiin sidoo kale waa ka awood badan yihiin oo ka badan yihiin unugyada CAR-T ee markii hore la sameeyay. Waa nidaam teknoolojiyad sare oo qurux badan wax walba oo la tixgeliyo. "
Mackall waa qoraaga sare ee daraasadda waxaana lagu daabacay online Abriil 27 ee joornaalka Cell. Qoraaga koowaad ee daraasadda waa Louai Labanieh, oo ah arday qalin jabisay.
Sida laga soo xigtay Labanieh, "Waxaan la yaabay heerka ay unugyada SNIP CAR-T uga fiicnaayeen daaweynta caadiga ah ee CAR-T." "Unugyada SNIP CAR-T waxay si buuxda u daaweeyeen jiirarka leh burooyinka adag ee lafaha iyo habdhiska dareenka," taas oo ka soo horjeeda daaweynta caadiga ah ee CAR-T, taas oo ahayd mid dhamaystiran.
Because the FDA has already given its blessing to the oral medication that stimulates the activity of the SNIP CAR-T cells, the researchers are optimistic that they will be able to begin clinical trials in people who have solid tumours within the next 24 months.
Gelida unugyada difaaca si ay u shaqeeyaan
Unugyada CAR-T waa unugyo difaac ah oo loo yaqaanno unugyada T kuwaas oo laga soo ururiyey bukaanka oo hidde ahaan loogu farsameeyey shaybaar si loo aqoonsado oo loo weeraro unugyada kansarka oo wata unug gaar ah oo korkooda ku yaal. Unugyadan ayaa markaa loo isticmaalaa in lagu sameeyo unugyo CAR-T. Unugyada CAR-T ayaa markaa loo isticmaali karaa in lagu daweeyo bukaannada. Taas ka dib, antigens-ka ayaa dib loogu soo celinayaa bukaanka si loola dagaallamo cudurka. Marka soo-dhoweeyaha unugga CAR-T uu ku xidho bartilmaameedka unugga kansarka, waxa uu bilaabaa fal-celinta silsiladda gudaha unugga CAR-T oo u dira calaamad unugga si uu u dilo unugga kansarka.
Maamulka Cuntada iyo Dawooyinka (FDA) ayaa oggolaaday bilowga isticmaalka daawaynta unugyada CAR-T ee 2017 ee daaweynta leukemia ba'an ee lymfoblastic ee carruurta iyo dadka waaweyn. Tan iyo markaas, waxaa sidoo kale loo oggolaaday isticmaalka dadka qaangaarka ah ee la ildaran noocyo kala duwan oo kansarka dhiigga ah, sida myeloma badan iyo noocyo kala duwan oo lymphoma ah. Unugyada CAR-T ee aqoonsada molecules kale ama laba bartilmaameed oo molecular halkii ay ka ahaan lahaayeen mid ayaa hadda tijaabinaya cilmi-baarayaashu. Qaabka asalka ah ee daawaynta waxa uu bartilmaameedsadaa molecule ku yaal dusha unugyada kansarka ee loo yaqaan CD19.
Labanieh’s goal was to design a CAR-T system that, once the cells had been transplanted back into the patient, could be easily monitored and adjusted. He did this by introducing a viral protein known as a protease into the CAR-T cells. The CAR-T receptor, which is located on the cytoplasmic side of the cell membrane, is cleaved by this protease, which in turn blocks the signalling cascade that initiates the killing activity of the cells. The protease can be rendered inactive by using the medication grazoprevir, which is authorised for use in the treatment of hepatitis C. The cells are dormant when the drug is not present, but as soon as it is there, they become active and start eliminating cancer cells from the body.
Maqnaanshaha grazoprevir, Labanieh iyo asxaabtiisu waxay muujiyeen in unugyada SNIP CAR-T ay noqdaan kuwo aan firfircoonayn oo ku jira jiirarka shaybaarka. Dhanka kale, protease-ka ayaa awooday in la xakameeyo oo unugyada SNIP CAR-T waxay awoodeen inay noqdaan kuwo firfircoon marka grazoprevir lagu maamulo jiirka afka. Qaabka jiirka ee sunta dilaaga ah ee ay keentay CAR-T, jiirarka lagu daweeyay unugyada SNIP CAR-T ayaa awooday inay soo kabtaan ka dib markii daawaynta grazoprevir la joojiyay. Tani waxay muujisay in nidaamku awood u leeyahay inuu u dhaqmo sidii beddel badbaado leh oo bukaannada ah marka loo eego daaweynta CAR-T ee caadiga ah.
Sida laga soo xigtay Labanieh, "dadaalladii hore ee lagu abuurayay unugyada CAR-T ee daroogada lagu maamuli karo waxay keeneen habab aad u jilicsan ama qulqulaya." Tani waa markii ugu horeysay ee aan awoodno inaan hagaajinno waxqabadkooda illaa heer gaar ah.
Intaa waxaa dheer, Mackall wuxuu sheegay in "marka nidaamka SNIP CAR-T ee leh qiyaasta grazoprevir ee buuxa uu shido, wuxuu ku socdaa awood buuxda." "Oo mar alla markii grazoprevir uu baxo, ma jirto daaweyn kale. Tani aad ayey muhiim ugu tahay bukaanada la ildaran sunta. Waxaan awood u leenahay inaan ka joojino unugyada inay soo baxaan, taasoo iibsan karta bukaanka waqti si uu u fiicnaado. Inta badan furayaasha kale ee badbaadada waxaa loogu talagalay in la baabi'iyo gebi ahaanba unugyada CAR-T ama si joogto ah loo damiyo. Waxaa suurtogal ah in bukaanku uu ka gudbo daawaynta, laakiin kama bogsan doonaan kansarka.
Daaweynta burooyinka adag
Markii cilmi-baarayaashu ay tijaabiyeen awoodda unugyada SNIP CAR-T si ay ula dagaallamaan kansarka adag ee jiirarka, waxay ogaadeen inay aad uga waxtar badan yihiin daaweynta CAR-T ee caadiga ah. Xaalado badan, cilmi-baarayaashu waxay awoodeen inay daaweeyaan jiirarka lahaa kansarka maskaxda ee loo yaqaan medulloblastoma ama kansarka lafaha loo yaqaan osteosarcoma.
Si lama filaan ah, waxay sidoo kale ogaadeen in hagaajinta qiyaasta grazoprevir ay ka dhigtay unugyada CAR-T mid midab-takoor ah, iyaga oo hagaya dhaqdhaqaaqooda dilka unugyada kansarka leh heerarka sare ee molecule bartilmaameedka ah iyada oo la ilaalinayo nudaha caadiga ah ee leh heerarka hoose ee molecule isku mid ah. Tani waxay ahayd daahfurid muhiim ah sababtoo ah waxay sharraxaysaa sida unugyada CAR-T u awoodeen inay kala saaraan unugyada kansarka iyo unugyada caadiga ah. Sida laga soo xigtay cilmi-baarayaasha, awoodda injineernimada unugyada CAR-T si ay u aqoonsadaan molecules bartilmaameedka ee sidoo kale ku jira unugyada caafimaadka qaba waxay awood u leeyihiin inay si weyn u wanaajiyaan awoodda qofku u leeyahay inuu la dagaallamo burooyinka adag ee bini'aadamka.
Mackall waxa uu suurtogalnimadan ku tilmaamay “suurtogal dhab ah oo soo jiidasho leh.” "Haddii aan awoodno inaan hoos u dhigno waxqabadka unugyada SNIP CAR-T si fudud annaga oo hagaajineyna qiyaasta grazoprevir, markaa waxaan awood u yeelan doonnaa inaan si sax ah u gaarno daaweynta bukaan kasta. Tani waxay ka hortagi doontaa sunta ama waxay kaxayn doontaa unugyada CAR-T si ay u dilaan unugyada kansarka halkii ay ka ahaan lahaayeen unugyo caadi ah. Waxaan aaminsanahay in daawaynta kansarka ay tahay midda jiilka soo socda oo ay wax ka beddeli doonto goobta unugyada CAR-T.
Qorayaasha kale ee ka socda Stanford waxaa ka mid ah Robbie Majzner, MD, kaaliyaha borofisar ee cudurrada carruurta; Culimada postdoctoral Dorota Klysz iyo Sean Yamada-Hunter, PhD; saynis yahan sare oo cilmi baadhis ah oo lagu magacaabo Elena Sotillo, PhD; cilmi-baarayaasha cilmiga nolosha Chris Fisher, Kaithlen Pacheco, Meena Malipatlolla, Johanna Theruvath, iyo Peng Xu, MD, PhD; Jose Vilches-Moure, DVM, PhD,
This study was made possible with funding from the National Institutes of Health (grants U54 CA232568-01, DP2 CA272092, and U01CA260852), the National Science Foundation, Stand Up 2 Cancer, the Parker Institute for Cancer Immunotherapy, Lyell Immunopharma, the Virginia and D.K. Ludwig Fund for Cancer Research, the Cancer Research Institute, German Cancer Aid, and others.
Marka la eego daraasadda, Labanieh, Mackall, Majzner, iyo Lin waxay dhammaantood ku taxan yihiin wada-hal-abuurayaal ku saabsan patent-ka. Mackall waa mid ka mid ah aasaasayaasha saddex shirkadood oo hadda ka shaqeynaya horumarinta daawaynta ku salaysan CAR-T. Shirkadahani waa Lyell Immunopharma, Sayniska Nolosha ee Isku-xirka, iyo Isku-xirka Daawaynta Unugyada. Labanieh waa lataliye u ah Syncopation Life Sciences marka lagu daro inuu yahay aasaasihii shirkadda. Labanieh, Majzner, Sotillo, iyo Weber dhamaantood waa la taliyayaal Lyell Immunopharma iyo sidoo kale saamilayda shirkadda.
Wixii macluumaad ah guji halkan.
