A kan wannan shafin za mu tattauna maganin antigen receptor (CAR) T-cell far.
Overview
Fahimtar CAR T-cell far a cikin lymphoma
Dr Michael Dickinson, Peter MacCallum Cancer Center
Chimeric antigen receptor (CAR) T-cell far wani nau'in immunotherapy ne wanda ke amfani da tsarin garkuwar jikin mutum don ƙoƙarin lalata ƙwayoyin lymphoma.
Tsarin garkuwar jiki yakan kare mu kuma shine garkuwar jiki daga kamuwa da cututtuka, gami da kansa. Ya ƙunshi cibiyar sadarwa na gabobin jiki da ƙwararrun ƙwayoyin jinin jini da ake kira lymphocytes. Akwai nau'ikan lymphocytes guda uku waɗanda suka haɗa da:
- B-lymphocytes (B-cells) - wanda ke yin rigakafi don yaƙar kamuwa da cuta
- T-lymphocytes (T-cells) - Taimakawa sel B don yin rigakafi don gano ƙwayoyin cuta, yaƙar kamuwa da cuta da kashe ƙwayoyin cuta ko ƙwayoyin kansa kai tsaye a cikin jiki.
- Kwayoyin kisa na halitta (NK). – Har ila yau suna kai hari kan ƙwayoyin kansa, ƙwayoyin cuta da kashe ƙwayoyin cuta
Lokacin da lymphocytes suka sami wasu canje-canje na kwayoyin halitta, suna rarraba kuma suna girma ba tare da kulawa ba wanda zai haifar da lymphoma. Wannan yana haifar da tsarin garkuwar jiki ba zai iya gano kwayoyin cutar kansa ba ko kuma rashin iya lalata su. Kwayoyin ciwon daji kuma na iya haɓaka hanyoyin da za su hana tsarin rigakafi daga kai musu hari. Misali, wasu kwayoyin cutar kansa suna yin sunadaran sunadaran musamman a saman su wanda ke gaya wa T-cell kada su kai musu hari.
Chemotherapy da radiation far sun kasance hanyoyin gargajiya don magance ciwon daji. Immunotherapy wani nau'i ne na magani wanda ke inganta ikon jiki don ganowa da kuma kai hari ga kwayoyin cutar kansa ta hanyar amfani da tsarin garkuwar jiki.
yanki ne mai aiki na bincike na asibiti kuma akwai ingantattun jiyya na rigakafi. Waɗannan sun haɗa da maganin rigakafin ƙwayoyin cuta na monoclonal (rituximab ko obinutuzumab), sauran hanyoyin da aka yi niyya (misali. Pembrolizumab a cikin lymphoma Hodgkin da lymphoma na farko na mediastinal B-cell lymphoma), da kuma mafi kwanan nan chimeric antigen receptor (CAR) T-cell far.
Menene CAR T-cell far?
CAR T-cell far sabon nau'in rigakafi ne wanda ke amfani da ƙwayoyin T-cell na majiyyaci don ganewa da kai hari kan ƙwayoyin cutar kansa. CAR T-cell far yana amfani da ƙwayoyin T-cell da aka canza na musamman don kai tsaye da kai tsaye ga wasu cututtukan daji, gami da wasu nau'ikan ƙwayoyin lymphoma B-cell. Kwayoyin T da aka sake tsarawa suna ƙarfafa tsarin rigakafi don kai hari da kashe ƙwayoyin lymphoma.
Ana tattara kaso daga cikin ƙwayoyin T-majiyyacinsu daga jini ta amfani da hanyar da ake kira apheresis. Wadannan kwayoyin halitta an sake sabunta su a cikin wani dakin gwaje-gwaje na musamman, don haka yanzu suna dauke da sifofi na musamman da ake kira chimeric antigen receptors (CAR) a samansu. CARs sunadaran sunadaran da aka ƙera don haɗawa da takamaiman manufa akan ƙwayoyin cutar kansa. Don samfuran da aka amince da su a halin yanzu, ana kiran wannan furotin CD19 wanda ke samuwa a saman al'ada da ƙwayoyin B-ciwon daji.
Kwayoyin CAR T da aka ƙera ana sake shigar da su cikin majiyyaci (kamar ƙarin jini). Lokacin da suka ɗaure ga mai karɓar abin da suke so, sai su ninka cikin sauri, kuma suna kashe ƙwayoyin da aka yi niyya wanda a cikin wannan yanayin shine lymphoma na B-cell da na al'ada B lymphocytes. Suna ci gaba da haɓakawa kuma suna kai hari ga ƙwayoyin cutar kansa har sai sun shuɗe.
A wasu lokuta, ana tunanin cewa CAR T-cells suna ci gaba da rayuwa a cikin jiki (wanda ake kira "nacewa") kuma suna iya ci gaba da kiyaye lymphoma ko cutar sankarar bargo a bay. Wannan shine dalilin da ya sa mutane da yawa suna tunanin CAR T-cell a matsayin 'magungunan rai'.
Wanene ya cancanci maganin CAR T-cell?
CAR T-cell far ana ba da kuɗin jama'a a Ostiraliya don mutanen da suka cika ƙaƙƙarfan ƙa'idodin cancanta waɗanda ƙungiyar ƙwararrun likitocin za su bi. Marasa lafiya waɗanda aka gano tare da ɗaya daga cikin cututtukan da aka lissafa B-cell, waɗanda suka sake dawowa bayan aƙalla 2 kafin hanyoyin kwantar da hankali ko kuma sun ƙi (ba su amsa maganin chemotherapy ba) kuma suna da lafiya, suna iya cancanci samun CAR T-cell far. CAR T-cell far na iya samun mummunar illa kuma bai dace da kowa ba.
Yawancin marasa lafiya yawanci suna shiga cikin gafara bayan sun karɓi daidaitaccen tsarin layin farko na yanzu wanda yawanci ya haɗa da chemotherapy da maganin rigakafin monoclonal. CAR T-cell far yana da tsada sosai kuma yana kashe sama da $500,000 ga kowane majiyyaci. Babban farashi shine saboda ƙwararrun masana'antun masana'antu waɗanda ke da hannu don ƙirƙirar ƙwayoyin T-CAR. Wasu cibiyoyin ciwon daji ne kawai za a horar da su musamman don ba da maganin CAR T-cell da sarrafa kulawar haƙuri.
Wadannan ƙananan nau'ikan lymphoma na iya zama cancanta:
- Yada Manyan B-cell Lymphoma
- Canza Lymphoma Follicular
- Matsayi na 3b Follicular Lymphoma
- Na farko Mediastinal B-cell Lymphoma
- B-cell Acute Lymphoblastic Lymphoma (B-ALL) don mutanen da ba su wuce 26 ba
- Mantle Cell Lymphoma.
CAR T-cell far a Ostiraliya
A Ostiraliya, an sami samfura biyu waɗanda suka sami ingantacciyar shawara daga Kwamitin Ba da Shawarar Sabis na Kiwon Lafiya (MSAC) kuma nan ba da jimawa ba za a ba da kuɗin jama'a duka. Waɗannan samfuran sun haɗa da:
- KimiyaTM (tisagenlecleucel) samfurin Novartis kuma ana ba da kuɗin jama'a a Ostiraliya
- YascartaTM (axicabtagene ciloleucel) samfurin Gileyad kuma ana ba da kuɗin jama'a a Ostiraliya
- TecartusTM (brexucabtagene autoeucel) samfurin Gileyad wanda ake ba da tallafi ga jama'a a Ostiraliya.
Kwararrun likitoci sun tattauna duk shawarwarin a taron CAR T-cell na mako-mako. Don ƙarin bayani magana da likitan ku ko Lymphoma Australia.
A ina zan iya samun maganin CAR T-cell?
manya | yara |
Western Australia Asibitin Fiona Stanley New South Wales Asibitin Royal Prince Alfred Asibitin Westmead Victoria Cibiyar Ciwon daji ta Peter MacCallum Queensland Royal Brisbane da Asibitin Mata | Queensland Asibitin Yara na Queensland New South Wales Asibitin Yara Victoria Asibitin Royal Yara Hoton Alfred |
Tsarin T-cell na CAR
CAR T-cells ana yin su ne daban-daban ga kowane mutum. Kuna iya karɓar wasu jiyya, irin su chemotherapy (maganin gado), don kiyaye lymphoma a ƙarƙashin ikon ku yayin da ake yin ƙwayoyin T-CAR (makonni 3-6).
- Tarin T-cell: Ana ɗaukar jini daga majiyyaci. Kwayoyin farin jinin, waɗanda suka haɗa da ƙwayoyin T, an ware su kuma ana mayar da sauran jinin zuwa cikin jinin majiyyaci ta hanyar apheresis (kama da tattara kwayoyin halitta). Ana aika ƙwayoyin T-majiyyaci zuwa lab don kerawa.
- Kera CAR T-cells: T-cells an gyara su ko kuma an canza su ta hanyar kwayoyin halitta (canza) don su iya ganowa da kashe kwayoyin cutar kansa. T-cells na injiniyan yanzu ana kiran su CAR T-cells. Kwayoyin CAR T na majiyyaci suna ninka har sai an sami miliyoyin su sannan kuma a daskare su. Sannan ana mayar da ƙwayoyin T-CAR zuwa asibitin majiyyaci. Wannan tsari na iya ɗaukar makonni da yawa.
- Chemotherapy: Mai haƙuri zai karɓi maganin chemotherapy (lymphodepletion), don rage adadin ƙwayoyin T-sel na al'ada a cikin jiki don samar da sarari ga ƙwayoyin T-CAR, don haka zasu iya faɗaɗa ( ninka) sau ɗaya ana gudanarwa. Yawanci, wannan chemotherapy shine fludarabine da cyclophosphamide.
- CAR T-cell jiko: Ana narke ƙwayoyin CAR T na majiyyaci sannan a mayar da su cikin jinin majiyyaci, kama da samun ƙarin jini ko ƙwayoyin sel.
- A jikin mara lafiya: Kwayoyin CAR T suna karuwa da sauri a cikin jinin mara lafiya. CAR T-cell yana gano kuma yana kashe ƙwayoyin lymphoma. Kwayoyin T-CAR na iya zama a cikin jini don kai hari idan lymphoma ya dawo.
- Maidowa: Za a kula da majiyyaci a hankali yayin da kuma bayan jiyya. Marasa lafiya waɗanda suka karɓi maganin CAR T-cell suna da lokacin dawowa na kusan watanni 2-3. A wannan lokacin, za a kimanta marasa lafiya don sakamako masu illa da kuma amsa magani. A cikin aƙalla kwanaki 30 na farko bayan an sallame su daga asibiti, marasa lafiya suna buƙatar kasancewa kusa (a cikin minti 20) zuwa asibitin da suke jiyya don bibiya akai-akai ko kulawar gaggawa idan an buƙata.
Matsaloli masu yiwuwa na maganin CAR T-cell
Duk magunguna da maganin ciwon daji na iya haifar da illa. CAR T-cell far wani sabon nau'in magani ne, kuma kamar yadda masu bincike suka fahimci maganin da kyau, haka kuma sarrafa waɗannan illolin. CAR T-cell far na iya haifar da mummunar illa kuma ana ba da magani ne kawai a asibitoci tare da kayan aiki da ƙwararrun ma'aikata don sarrafa waɗannan sakamako masu kyau.
Yana da mahimmanci a lura cewa ba duka marasa lafiya ba ne za su iya jure wa wasu abubuwan da za su iya haifar da lahani don haka kowane majinyaci da yanayin lafiyar kowane majiyyaci yana buƙatar yin la'akari da hankali kafin yin maganin CAR T-cell.
Wasu daga cikin illolin na yau da kullun na iya shafar adadi mai yawa na marasa lafiya kuma suna iya haifar da tsawaita asibiti. Yawan waɗannan illolin na iya zama alaƙa da samfurin da aka yi amfani da su, da kuma abubuwan da ke da alaƙa da haƙuri da cuta. Waɗannan sun haɗa da:
- Ciwon saki na Cytokine
- Zazzabi da sanyi
- Ƙananan hawan jini da ƙananan matakan oxygen
- Matsalolin tsarin jijiya ciki har da; matsalolin kwakwalwa (encephalopathy), ciwon kai, jujjuyawa ko girgiza (jijjiga) ko dizziness
- Rapid zuciya rate (tachycardia) da canje-canje a cikin bugun zuciya (arrhythmia)
- Gajiya (matsananciyar gajiya)
- tari
- Alamun narkewa; tashin zuciya, amai, rage cin abinci, zawo da maƙarƙashiya
- Febrile neutropenia (ƙananan neutrophils - tsarin rigakafi) da cututtuka
Menene ciwon sakin cytokine (CRS)?
Ciwon saki na cytokine (CRS) wani sakamako ne mai yuwuwa mai tsanani kuma yana da alaƙa da CAR T-cell far. Cytokines su ne saƙon sinadarai waɗanda ke taimakawa T-cell don gudanar da ayyukansu, waɗanda ke samar da su lokacin da ƙwayoyin CAR T suka ninka cikin jiki kuma suna kashe ƙwayoyin cutar kansa. Alamun CRS na iya kamawa daga ƙananan mura kamar alamomi zuwa mafi tsanani bayyanar cututtuka.
Kwayoyin T an tsara su don saki cytokines (manzannin sunadarai), waɗanda ke taimakawa wajen tadawa da kuma jagorantar amsawar rigakafi. Game da CRS, akwai saurin sakin cytokines a cikin jini, wanda zai iya haifar da zazzaɓi mai haɗari da rage hawan jini. Hakanan ana iya sanin wannan da 'guguwar cytokine'.
Alamomin sakin cytokine
CRS na iya tasowa a cikin kwanaki 1 zuwa 5 bayan an sake shigar da ƙwayoyin T-CAR a cikin majiyyaci, kodayake yana iya faruwa makonni baya a wasu lokuta. Ga yawancin marasa lafiya, yanayin yana da sauƙi wanda za'a iya sarrafa shi tare da tallafi na tallafi da kulawa.
Alamomi da alamomi na iya haɗawa da:
- Fever
- gajiya
- Rashin ci
- Ciwon tsoka da haɗin gwiwa
- Nuna da zubar
- cutar gudawa
- Rashes
- Saurin numfashi
- Rapid zuciya kudi
- Low jini
- seizures
- ciwon kai
- Rudewa ko hayyaci
- Majalisa
- tremor
- Rashin daidaituwa
Maganin ciwon saki na cytokine
Ga marasa lafiya da yawa, ana iya sarrafa CRS tare da daidaitattun hanyoyin kwantar da hankali kamar su steroids ko ruwan jijiya. Kamar yadda masu bincike suka sami ƙarin ƙwarewa tare da CAR T-cell far, suna koyon yadda za su iya sarrafa mafi tsanani lokuta na CRS.
Daidaitaccen magani ga marasa lafiya don sarrafa CRS mai tsanani shine ta hanyar ba da magani da ake kira tocilizumab (Actemra)TM). Wannan magani ne da aka sani a baya don magance wasu yanayi masu kumburi, wanda ake amfani dashi don toshe cytokine mai suna IL-6. IL-6 shine cytokine wanda aka ɓoye a cikin manyan matakan T-cell don mayar da martani ga kumburi.
Wasu marasa lafiya suna buƙatar shigar da su don kula da abubuwan da ke haifar da lahani kuma suna iya kasancewa a asibiti na mako guda ko makamancin haka. Wasu marasa lafiya suna buƙatar shigar da su don ƙarin tallafi a cikin sashin kulawa mai zurfi (ICU).
Matsalolin tsarin jijiya
Yawancin mutanen da aka yi wa maganin CAR T-cell na iya fuskantar matsalolin tsarin juyayi a cikin 'yan kwanaki na jiyya, kodayake matsalolin na iya tasowa har zuwa makonni 8 bayan jiyya. Matsalolin tsarin jijiya yawanci suna da sauƙi kuma suna samun sauki sama da makonni biyu.
Matsalolin da aka fi sani da su na iya shafar hanyar da kwakwalwar ku ke aiki, inda alamun cututtuka na iya haɗawa da rawar jiki, ciwon kai, rudani, asarar ma'auni, matsalar magana, tashin hankali da kuma wani lokacin hallucination. Wadannan illolin gabaɗaya suna raguwa bayan ƴan kwanaki, kodayake wasu na iya ɗaukar makonni.
Farfadowa na CAR T-cell far
Farfadowa na iya ɗaukar lokaci yayin da tsarin garkuwar marasa lafiya ya murmure. Matsakaicin lokacin dawowa da kulawa na kusa shine yawanci kwanaki 30 bayan jiko T-cell CAR. A wannan lokacin dole ne marasa lafiya su kasance a cikin mintuna 20 na cibiyar kula da cutar kansa. Dole ne su kasance suna da mai kula da su a kowane lokaci don lura da alamun zazzabi, kamuwa da cuta da matsalolin ƙwayoyin cuta. Yawancin marasa lafiya suna jin gajiya kuma ba sa samun ci sosai a wannan lokacin.
illar tsarin rigakafi
Kamar yadda CAR T-cell far ke shafar tsarin garkuwar jikin ku, za ku iya kasancewa cikin haɗarin kamuwa da cuta, gami da cututtuka masu tsanani bayan jiyya. Kwayoyin jinin ku na iya zama ƙasa, kuma wasu mutane suna da ƙananan matakan B-cell da ƙananan matakan antibody (maganin rigakafi sune sunadaran da kwayoyin B suke samarwa don taimaka maka yaki da kamuwa da cuta). Waɗannan matsalolin na iya sa jikinka ya yi wahala yaƙar cututtuka. Ana iya ba ku magani don taimakawa hana cututtuka. Idan kuna da ƙananan matakan rigakafi, kuna iya buƙatar maganin maye gurbin immunoglobulin (jiko na rigakafi) don taimakawa haɓaka tsarin rigakafi.
Gwajin asibiti a Ostiraliya
Akwai gwaje-gwaje na asibiti da yawa waɗanda a halin yanzu ake gudanar da su a duniya don adadin kansar jini daban-daban da kuma ƙanƙara. An nuna cewa ya fi nasara a wasu ƙwayoyin lymphomas B-cell. A halin yanzu akwai gwaji na asibiti don lymphoma B-cell a duk faɗin Ostiraliya akwai (daga jiyya ta farko) don:
- Yada manyan B-cell lymphoma
- Litfirital lymphoma
- Mantle cell lymphoma
- B-cell wanda ba Hodgkin lymphoma
- Lymphocytic cutar sankarar bargo
Don ƙarin bayani duba shafin yanar gizon 'Fahimtar Gwajin Magunguna' ko duba www.clinicaltrials.gov
Gwaje-gwaje na asibiti na duniya
Akwai gwaje-gwajen asibiti da yawa don CAR T-cell far a duk duniya. Manyan ƙasashe a cikin ci gaba da gwaji na asibiti suna cikin Amurka da Turai. Akwai gwaje-gwajen asibiti da ke duban nau'ikan lymphomas da cutar sankarar bargo daga jiyya ta gaba, da kuma a cikin koma baya ko saiti.
Gwaje-gwaje na asibiti don CAR T-cell far a cikin mutane sun fara ne a cikin 2012. FDA (Hukumar Abinci da Magunguna a Amurka) kawai ta amince da ita a cikin 2017 wanda tun daga lokacin ya ga ci gaba da sauri a duniya a cikin amfani da CAR T-cell far.
Masu bincike har yanzu suna ƙoƙarin fahimtar yadda wannan maganin ke aiki, inganta tasirin sakamako da inganta sakamako ga marasa lafiya. Wani yanki ne mai tasowa cikin sauri na bincike da ban sha'awa yadda aka yi nisa cikin kankanin lokaci.
Don ƙarin bayani duba shafin yanar gizon 'Fahimtar Gwajin Magunguna' ko duba www.clinicaltrials.gov
Domin karin bayani
- Yi magana da likitan ku game da ko kun cancanci ko kun dace don samun maganin CAR T-cell. Idan haka ne, likitan ku na jini zai iya shirya mai ba da shawara.
- Don kowace tambaya da ke da alaƙa da cancantar haƙuri don maganin CAR T-cell ko yadda marasa lafiya za su iya samun damar wannan jiyya, da fatan za a yi imel: CAR-T.enquiry@petermac.org
- Kuna iya tuntuɓar Layin Tallafin Nurse na Lymphoma: T 1800 953 081 ko imel: nurse@lymphoma.org.au don ƙarin bayani ko shawara.
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