June 2022: Zvinoenderana nezvakawanikwa muongororo ichangobva kuburitswa na Stanford Mushonga mumakonzo, kurapwa kwegomarara kunoshandisa ega ega ega masero emuviri ekudzivirira chirwere chemurwere kuti arwise maseru egomarara akachengeteka uye anoshanda zvakanyanya kana achigona kuvhurwa nekudzimwa nemushonga wemukanwa.
Kurapa kwekutanga, uko kwava kunzi CAR-T cell therapy, kwakaratidza kubudirira kunoshamisa mukurwisa marudzi akasiyana egomarara reropa. Nekudaro, nekuda kwekuti vamwe varwere vane immune reaction kumasero akagadzirwa anogona kuuraya, kurapwa kweCAR-T kunowanzo kuchengeterwa kushandiswa chete mushure mekunge mamwe marapirwo atanga aongororwa.
Yakavewo nehuwandu hwekubudirira mukurapa varwere vane mamota akasimba, akadai seanowanikwa mugomarara reuropi nemapfupa. Vatsvakurudzi vanotenda kuti izvi zvinokonzerwa nekuti masero eCAR-T anotapukirwa nekugamuchira kuwanda kwechiratidzo, izvo zvinoita kuti vapedzisire vasati vapedza mamota akasimba. Mukuwedzera, kusiyana nekenza yeropa, zvakaoma kuziva ma molecular targets pamamota akasimba. Izvi zvinonangwa nemamorekuru zvinofanirwa kunge zviripo chete pamaseru egomarara uye kwete pamatishu akajairwa kuitira kuti ive nzira dzekurapa dzinoshanda.
Vatsvagiri vekuStanford vakauya neyakagadziridzwa CAR-T cell therapy yavanodaidza kuti SNIP CAR-T. Kurapa uku kunoitwa nekutora mushonga wepamuromo wehepatitis uyo Food and Drug Administration yakatopa mwenje wegirini kuti ushandiswe muvanhu. (Masero eSNIP CAR-T haashande kana mushonga ukasapihwa.)
Vaya varwere vari panjodzi yekuva neakaipa kune maseru akagadziridzwa anodzivirirwa nefoilsafe mechanism inonzi kugona kushandisa mushonga kugadzirisa chiyero chebasa remasero mushure mekunge vadzoserwa mumurwere. Vatsvagiri vakawanawo kuti masero akagadziridzwa eCAR-T ainyanya kushanda mukurwisa gomarara rakasimba mumakonzo emurabhoritari. Vanofungidzira kuti izvi zvingave zvakadaro nekuti masero akawana nguva pfupi uye yakadzokororwa yekuzorora apo mushonga wezuva nezuva waiitwa metabolised mumitumbi yemhuka.
Crystal Mackall, MD, Ernest naAmelia Gallo Mhuri Purofesa pamwe napurofesa wevana uye wemishonga, vakataura kuti vakagadzira "remote-controlled" CAR-T therapy iyo inogona kugadzirirwa kune mumwe nomumwe murwere. “Masero eCAR-T aya akagadziridzwa haangochengeteki chete, asi ane simba uye anogona kuita zvakasiyana-siyana kupfuura masero eCAR-T akatanga kugadzirwa. Iyo yakanaka yepamusoro-tech system zvinhu zvese zvinotariswa. "
Mackall ndiye munyori mukuru wechidzidzo ichi uye chakaburitswa online muna Kubvumbi 27 mujenari Cell. Munyori wekutanga wechidzidzo ichi ndiLouai Labanieh, uyo ari mudzidzi akapedza kudzidza.
Sekureva kwaLabanieh, "Ndakashamiswa nedanho rekuti masero eSNIP CAR-T aive nani pane kurapa kwakajairika kweCAR-T." "SNIP CAR-T masero akaporesa zvachose mbeva dzine mazamu akasimba mumapfupa uye hurongwa hwemitsipa," mukusiyana nemishonga yakajairika yeCAR-T, iyo yakanga yakundikana zvachose.
Nekuti iyo FDA yakatopa chikomborero chayo kumushonga wemukanwa unomutsa basa reSNIP CAR-T masero, vaongorori vane tarisiro yekuti vachakwanisa kutanga miedzo yekiriniki muvanhu vane mabundu akasimba mukati memwedzi makumi maviri nemana inotevera.
Kuisa masero emuviri kushanda
Masero eCAR-T maseru edziviriro anonzi T masero anounganidzwa kubva kumurwere uye anogadzirwa genetic murabhoritari kuti azive uye kurwisa cancer maseru ane chaiwo mamorekuru paari. Masero aya anobva ashandiswa kugadzira masero eCAR-T. Masero eCAR-T anogona kuzoshandiswa kurapa varwere. Mushure meizvi, maantigen anodzoserwa mumurwere kuitira kurwisa chirwere. Kana iyo receptor iri pa CAR-T sero inosunga kune chinangwa pasero regomarara, inokanda ketani mukati meCAR-T cell iyo inotumira chiratidzo kune sero kuuraya kenza sero.
Chikafu neDrug Administration (FDA) yakapa mvumo yekutanga yekushandiswa kweCAR-T cell therapy muna 2017 yekurapa acute lymphoblastic leukemia muvana nevakuru vechidiki. Kubva ipapo, yakabvumidzwawo kuti ishandiswe kune vanhu vakuru vanorwara nemhando dzakasiyana dzekenza yeropa, senge multiple myeloma uye mashoma akasiyana marudzi e lymphoma. Masero eCAR-T anoziva mamwe mamorekuru kana maviri mamorekuru anotariswa pachinzvimbo cheimwe ari kuedzwa nevanoongorora. Iyo yekutanga fomu yekurapa inonangana nemorekuru pamusoro pemaseru egomarara anonzi CD19.
Chinangwa chaLabanieh chaive chekugadzira CAR-T system iyo, kana maseru aiswazve mumurwere, aigona kutariswa nekugadziriswa zviri nyore. Akaita izvi nekuisa puroteni yehutachiona inozivikanwa seprotease mumasero eCAR-T. Iyo CAR-T receptor, iyo iri padivi recytoplasmic ye cell membrane, yakatsemurwa neiyi protease, iyo inovhara iyo inonongedza cascade inotanga basa rekuuraya remasero. Iyo protease inogona kuitwa isingashande nekushandisa mushonga wegrazoprevir, iyo inobvumirwa kushandiswa mukurapa hepatitis C. Masero akarara kana mushonga usipo, asi kana uchangovapo, anova anoshanda uye anotanga kubvisa kenza. masero kubva mumuviri.
Mukushaikwa kwegrazoprevir, Labanieh nevamwe vake vakaratidza kuti masero eSNIP CAR-T haashande mumakonzo emurabhoritari. Kune rimwe divi, protease yakakwanisa kuvharirwa uye masero eSNIP CAR-T akakwanisa kushandiswa apo grazoprevir yakaitwa kumakonzo nemuromo. Mumuenzaniso wembeva weCAR-T-induced lethal toxicity, mbeva dzakarapwa neSNIP CAR-T masero dzakakwanisa kupora mushure mekunge kurapwa kwegrazoprevir kwakamiswa. Izvi zvakaratidza kuti sisitimu iyi ine mukana wekuita seimwe nzira yakachengeteka kune varwere pane yakajairika CAR-T kurapwa.
Sekureva kwaLabanieh, "nhamburiko dzakapfuura dzekugadzira masero eCAR-T anodzorwa nezvinodhaka dzakaburitsa masisitimu angave akaoma kana kuti asina kubuda." Aka ndekekutanga chaizvo kuti takakwanisa kugadzirisa basa ravo kusvika pamwero wakadaro.
Pamusoro pezvo, Mackall akataura kuti "kana iyo SNIP CAR-T system ine yakazara dosi grazoprevir iripo, ine simba rakazara." “Uye kana grazoprevir yapera, hapasisina kurapwa. Izvi zvakakosha kune varwere vane toxicosis. Isu tine kugona kumisa maseru kuberekana, izvo zvaizotengera murwere imwe nguva kuti ave nani. Ruzhinji rwemamwe ma switch ekuchengetedza anoitirwa kubvisa masero eCAR-T zvachose kana kudzima zvachose. Zvinogoneka kuti murwere achazviita kuburikidza nekurapa, asi ivo havazorapike gomarara ravo.
Kurapa kwemamota akasimba
Apo vatsvakurudzi vakaedza kukwanisa kweSNIP CAR-T masero kurwisana negomarara rakasimba mumakonzo, vakaona kuti ainyanya kushanda kupfuura kurapa kwakajairika kweCAR-T. Muzviitiko zvakawanda, vaongorori vakakwanisa kurapa mbeva dzaive nekenza yehuropi inozivikanwa se medulloblastoma kana kenza yepfupa inozivikanwa se osteosarcoma.
Tisingafungire, vakawanawo kuti kugadzirisa dosi yegrazoprevir kwakaita kuti masero eCAR-T awedzere kusarura, achitungamira basa ravo rekuuraya kumaseru egomarara ane mazinga akakwira emorekuru anotangwa uku achichengetedza matishu akajairwa ane mazinga akaderera emorekuru rimwe chete. Uku kwaive kuwanikwa kwakakosha nekuti kunotsanangura kuti masero eCAR-T akakwanisa sei kusiyanisa pakati pemaseru egomarara uye matishu akajairwa. Sekureva kwevatsvagiri, kugona kweinjiniya CAR-T maseru kuona mamorekuru anonangwa aripowo pamaseru ane hutano ane mukana wekuvandudza zvakanyanya kugona kwemunhu kurwisa mamota akasimba emunhu.
Mackall akaratidzira mukana uyu se "mukana unoyevedza". “Kana tikakwanisa kudzikisira kuita kwemasero eSNIP CAR-T nekungogadzirisa dhamo regrazoprevir, tinozokwanisa kunyatsoita kurapa kwemurwere wega wega. Izvi zvinogona kudzivirira huturu kana kutyaira masero eCAR-T kuuraya maseru egomarara kwete matishu akajairwa. Isu tinotenda kuti kurapwa kwegomarara uku ndekwechizvarwa chinotevera uye kuchashandura CAR-T cell field.
Vamwe vanyori vanobva kuStanford vanosanganisira Robbie Majzner, MD, mubatsiri wepurofesa wezvirwere zvevana; nyanzvi dzepashure Dorota Klysz naSean Yamada-Hunter, PhD; musayendisiti mukuru wekutsvakurudza anonzi Elena Sotillo, PhD; vatsvakurudzi vesayenzi yehupenyu Chris Fisher, Kaithlen Pacheco, Meena Malipatlolla, Johanna Theruvath, uye Peng Xu, MD, PhD; Jose Vilches-Moure, DVM, PhD,
Chidzidzo ichi chakaitwa kuti chigoneke nemari kubva kuNational Institutes of Health (zvipo U54 CA232568-01, DP2 CA272092, uye U01CA260852), National Science Foundation, Stand Up 2 Cancer, Parker Institute for Cancer Immunotherapy, Lyell Immunopharma, the Virginia uye DK Ludwig Fund yeCancer Research, Cancer Research Institute, German Cancer Aid, nevamwe.
Nezvechidzidzo ichi, Labanieh, Mackall, Majzner, naLin vese vakanyorwa sevakabatanidzwa pamwe patent. Mackall ndomumwe wevakatanga makambani matatu ari kushanda pakugadzira mishonga yeCAR-T-based. Makambani aya Lyell Immunopharma, Syncopation Life Sciences, uye Link Cell Therapies. Labanieh chipangamazano weSyncopation Hupenyu Sayenzi mukuwedzera pakuva muvambi wekambani. Labanieh, Majzner, Sotillo, uye Weber vese varairidzi veLyell Immunopharma pamwe nevanogovanisa mukambani.
Kuti uwane ruzivo tinya pano.
