Yuni 2022: Bisa ga sakamakon binciken da aka buga kwanan nan Magungunan Stanford a cikin beraye, maganin ciwon daji wanda ke yin amfani da ƙwayoyin rigakafi da aka gyara na majiyyaci don kai hari kan ƙwayoyin cutar kansa ya fi aminci kuma mafi inganci lokacin da magani na baka zai iya kunna shi da kashe shi.
Magani na farko, wanda a yanzu ake kira da CAR-T cell far, ya nuna gagarumar nasara wajen yaƙar cututtukan daji na jini iri-iri. Duk da haka, saboda gaskiyar cewa wasu marasa lafiya suna da maganin rigakafi ga sel injiniyoyi waɗanda ke da yuwuwar mutuwa, ana keɓance maganin CAR-T don amfani kawai bayan an fara bincikar wasu jiyya.
Haka kuma an samu raguwar nasara wajen kula da majinyatan da ke da tsattsauran ciwace-ciwace, kamar wadanda ake samu a cikin ciwon daji na kwakwalwa da kashi. Masu bincike sun yi imanin cewa hakan ya faru ne saboda gaskiyar cewa ƙwayoyin CAR-T suna da wuyar samun adadin sigina mai yawa, wanda ke sa su gaji kafin su iya kawar da ciwace-ciwacen daji. Bugu da ƙari, ya bambanta da ciwon daji na jini, yana da wuya a gano maƙasudin kwayoyin halitta akan ciwace-ciwacen ƙwayoyi. Wadannan makasudin kwayoyin dole ne su kasance a kan kwayoyin cutar kansa kawai ba a kan nama na al'ada ba don zama ingantaccen zaɓuɓɓukan magani.
Masu bincike a Stanford sun fito da wani gyare-gyare na CAR-T cell far da suke kira SNIP CAR-T. Ana kunna wannan maganin ta hanyar shan maganin hanta na baka wanda Hukumar Abinci da Magunguna ta riga ta ba da hasken kore don amfani a cikin mutane. (Kwayoyin SNIP CAR-T ba su da aiki idan ba a gudanar da maganin ba.)
Waɗancan marasa lafiya waɗanda ke cikin haɗarin samun mummunan sakamako ga sel ɗin da aka gyaggyarawa ana kiyaye su ta hanyar rashin aminci da ake kira ikon yin amfani da magani don daidaita matakin ayyukan sel bayan an dawo da su cikin majiyyaci. Masu binciken sun kuma gano cewa gyare-gyaren ƙwayoyin CAR-T sun fi tasiri sosai wajen yaƙar ciwon daji a cikin berayen dakin gwaje-gwaje. Suna tunanin cewa hakan na iya faruwa saboda sel sun sami ɗan taƙaitaccen lokaci da maimaita hutu yayin da magungunan yau da kullun ke narkewa a jikin dabbobi.
Crystal Mackall, MD, Farfesa na Iyali na Ernest da Amelia Gallo da kuma farfesa a fannin ilimin yara da kuma likitanci, sun bayyana cewa sun ɓullo da "masu sarrafawa" CAR-T farfesa wanda za a iya keɓancewa ga kowane majiyyaci. “Wadannan ƙwayoyin CAR-T da aka gyara ba kawai sun fi aminci ba, amma kuma sun fi ƙarfi da ƙarfi fiye da ƙwayoyin CAR-T waɗanda aka ƙirƙira tun asali. Kyakkyawan tsarin fasaha ne duk abin da aka yi la'akari da shi."
Mackall shine babban marubucin binciken kuma an buga shi akan layi a ranar 27 ga Afrilu a cikin mujallar Cell. Marubucin farko na binciken shine Louai Labanieh, wanda dalibi ne da ya kammala karatun digiri.
A cewar Labanieh, "Na yi mamakin matakin da SNIP CAR-T sel suka fi maganin CAR-T na al'ada." "Kwayoyin SNIP CAR-T sun warkar da mice gaba daya tare da ciwace-ciwacen daji a cikin kasusuwa da tsarin juyayi," ya bambanta da maganin CAR-T na al'ada, wanda ya kasance cikakkiyar gazawa.
Domin FDA ta riga ta ba da albarkar ta ga maganin baka wanda ke motsa ayyukan SNIP CAR-T Kwayoyin, masu bincike suna da kyakkyawan fata cewa za su iya fara gwajin gwaji a cikin mutanen da ke da ciwon ciwace-ciwace a cikin watanni 24 masu zuwa.
Sanya ƙwayoyin rigakafi suyi aiki
Kwayoyin CAR-T su ne ƙwayoyin rigakafi da ake kira T cell waɗanda aka tattara daga majiyyaci kuma an tsara su ta hanyar kwayoyin halitta a cikin dakin gwaje-gwaje don ganewa da kuma kai farmaki ga kwayoyin cutar kansa tare da takamaiman kwayoyin halitta a saman su. Ana amfani da waɗannan ƙwayoyin don yin ƙwayoyin CAR-T. Ana iya amfani da ƙwayoyin CAR-T don kula da marasa lafiya. Bayan haka, an sake dawo da antigens a cikin majiyyaci don yaki da cutar. Lokacin da mai karɓar tantanin halitta na CAR-T ya ɗaure zuwa ga manufa akan kwayar cutar kansa, yana farawa sarkar amsawa a cikin cell CAR-T wanda ke aika sigina zuwa tantanin halitta don kashe kwayar cutar kansa.
Cibiyar Abinci da Magunguna (FDA) ta ba da izini na farko don amfani da CAR-T cell far a cikin 2017 don maganin cutar sankarar lymphoblastic mai tsanani a cikin yara da matasa. Tun daga wannan lokacin, an kuma yarda da shi don amfani a cikin manya waɗanda ke fama da wasu nau'ikan ciwon daji na jini, irin su myeloma da yawa da wasu nau'ikan lymphoma daban-daban. Kwayoyin CAR-T waɗanda ke gane wasu ƙwayoyin cuta ko maƙasudin kwayoyin halitta guda biyu maimakon ɗaya a halin yanzu masu bincike suna gwada su. Asalin nau'in jiyya yana hari kan kwayar halitta a saman ƙwayoyin cutar kansa da ake kira CD19.
Manufar Labanieh ita ce tsara tsarin CAR-T wanda, da zarar an sake dasa sel cikin majiyyaci, za a iya sa ido cikin sauƙi da daidaita su. Ya yi haka ta hanyar shigar da furotin mai hoto ko bidiyo mai zagaya yanar gizo da sauri da aka sani da protease a cikin ƙwayoyin CAR-T. Mai karɓar mai karɓar CAR-T, wanda ke gefen cytoplasmic na membrane cell, yana katse shi da wannan furotin, wanda hakan ya toshe kasidar siginar da ke fara kashe ayyukan sel. Protease na iya zama mara aiki ta hanyar amfani da maganin grazoprevir, wanda aka ba da izini don amfani da shi wajen maganin ciwon hanta na C. Kwayoyin suna barci lokacin da miyagun ƙwayoyi ba su kasance ba, amma da zaran ya kasance a can, sun fara aiki kuma sun fara kawar da ciwon daji. Kwayoyin daga jiki.
Idan babu grazoprevir, Labanieh da abokan aikinsa sun nuna cewa ƙwayoyin SNIP CAR-T sun zama marasa aiki a cikin berayen dakin gwaje-gwaje. A gefe guda, an iya hana protease kuma ƙwayoyin SNIP CAR-T sun iya kunna lokacin da aka yi amfani da grazoprevir ga mice a baki. A cikin samfurin linzamin kwamfuta na CAR-T mai guba mai kisa, berayen da aka yi musu magani tare da ƙwayoyin SNIP CAR-T sun sami damar murmurewa bayan an daina maganin grazoprevir. Wannan ya nuna cewa tsarin yana da yuwuwar yin aiki azaman madadin mafi aminci ga marasa lafiya fiye da na CAR-T na al'ada.
A cewar Labanieh, "kokarin da aka yi a baya don ƙirƙirar ƙwayoyin CAR-T da za a iya sarrafa magunguna sun samar da tsarin da ko dai sun yi ƙanƙara sosai ko kuma suna zube." Wannan shine karo na farko da muka sami damar daidaita ayyukansu zuwa wani takamaiman matakin.
Bugu da kari, Mackall ya bayyana cewa "lokacin da tsarin SNIP CAR-T tare da cikakken adadin grazoprevir ke kunne, yana kan cikakken iko." “Kuma da zarar grazoprevir ya tafi, babu sauran magani. Wannan yana da mahimmanci ga marasa lafiya waɗanda ke fama da guba. Muna da ikon dakatar da sel daga haifuwa, wanda zai sayi majinyacin lokaci don samun lafiya. Yawancin sauran masu kashe aminci ana nufin ko dai su kawar da ƙwayoyin CAR-T gaba ɗaya ko kashe su na dindindin. Mai yiyuwa ne majiyyaci za su yi ta hanyar magani, amma ba za su warke daga cutar kansa ba.
Maganin m ciwace-ciwacen daji
Lokacin da masu binciken suka gwada ƙarfin ƙwayoyin SNIP CAR-T don yaƙar ciwon daji masu ƙarfi a cikin berayen, sun gano cewa sun fi tasiri fiye da maganin CAR-T na al'ada. A lokuta da yawa, masu binciken sun iya warkar da berayen da ke da ciwon daji na kwakwalwa da aka sani da medulloblastoma ko ciwon daji na kashi da aka sani da osteosarcoma.
Ba zato ba tsammani, sun kuma gano cewa daidaita kashi na grazoprevir ya sa ƙwayoyin CAR-T su zama masu nuna wariya, suna jagorantar ayyukan kashe su zuwa ga kwayoyin cutar kansa tare da manyan matakan kwayoyin da aka yi niyya yayin da suke kiyaye nama na al'ada tare da ƙananan matakan kwayoyin guda ɗaya. Wannan wani muhimmin bincike ne saboda yana bayyana yadda ƙwayoyin CAR-T suka iya bambanta tsakanin ƙwayoyin cutar kansa da nama na al'ada. A cewar masu binciken, iyawar injiniyoyin CAR-T na injiniya don gane ƙwayoyin da ke da niyya waɗanda kuma ke kan sel lafiya suna da yuwuwar inganta ƙarfin mutum na yaƙar ciwace-ciwacen ɗan adam.
Mackall ya bayyana wannan yuwuwar a matsayin "yiwuwar gaske mai ban sha'awa." "Idan za mu iya rage ayyukan sel na SNIP CAR-T ta hanyar daidaita kashi na grazoprevir, to za mu iya daidaita daidaitaccen maganin ga kowane mai haƙuri. Wannan zai hana guba ko kuma fitar da ƙwayoyin CAR-T don kashe ƙwayoyin cutar kansa maimakon nama na yau da kullun. Mun yi imanin cewa wannan maganin ciwon daji na zamani ne na gaba kuma zai kawo sauyi a filin CAR-T.
Sauran marubuta daga Stanford sun hada da Robbie Majzner, MD, mataimakiyar farfesa a fannin ilimin yara; malaman postdoctoral Dorota Klysz da Sean Yamada-Hunter, PhD; wani babban masanin kimiyyar bincike mai suna Elena Sotillo, PhD; masu binciken kimiyyar rayuwa Chris Fisher, Kaithlen Pacheco, Meena Malipatlolla, Johanna Theruvath, da Peng Xu, MD, PhD; Jose Vilches-Moure, DVM, PhD,
An yi wannan binciken tare da kudade daga Cibiyoyin Lafiya na Kasa (ba da U54 CA232568-01, DP2 CA272092, da U01CA260852), Cibiyar Kimiyya ta Kasa, Stand Up 2 Cancer, Parker Institute for Cancer Immunotherapy, Lyell Immunopharma, Virginia da kuma Asusun DK Ludwig don Binciken Ciwon daji, Cibiyar Nazarin Ciwon daji, Taimakon Ciwon daji na Jamus, da sauransu.
Dangane da binciken, Labanieh, Mackall, Majzner, da Lin duk an jera su a matsayin masu ƙirƙira a kan haƙƙin mallaka. Mackall yana ɗaya daga cikin masu haɗin gwiwar kamfanoni uku waɗanda ke aiki a halin yanzu don haɓaka hanyoyin kwantar da hankali na CAR-T. Waɗannan kamfanoni sune Lyell Immunopharma, Syncopation Life Sciences, da Link Cell Therapies. Labanieh mai ba da shawara ne na Syncopation Life Sciences baya ga kasancewarsa wanda ya kafa kamfanin. Labanieh, Majzner, Sotillo, da Weber duk masu ba da shawara ne na Lyell Immunopharma da masu hannun jari a kamfanin.
Don bayani danna nan.
