Kweli phepha siza kuxubusha i-chimeric antigen receptor (CAR) T-cell therapy.
isishwankathelo
Ukuqonda unyango lwe-CAR T-cell kwi-lymphoma
UGqr Michael Dickinson, iZiko loMhlaza likaPeter MacCallum
I-Chimeric antigen receptor (CAR) Unyango lwe-T-cell luhlobo lwe-immunotherapy esebenzisa i-immune system yomntu ukuze azame ukutshabalalisa iiseli ze-lymphoma.
Amajoni omzimba adla ngokusikhusela kwaye lukhuselo lomzimba kwizifo nakwizifo, kuquka umhlaza. Yenziwe ngothungelwano lwamalungu kunye neengcali zeeseli ezimhlophe zegazi ezibizwa ngokuba yi-lymphocytes. Kukho iintlobo ezintathu ze-lymphocytes ezibandakanya:
- I-lymphocytes (iiseli ze-B) – ezenza amajoni omzimba ukulwa usulelo
- T lymphocytes (T-cells) – nceda ii-B-cell zenze amajoni omzimba ukuchonga iiseli ezosulelekileyo, ukulwa usulelo kwaye zibulale ngokuthe ngqo iiseli ezosulelekileyo okanye zomhlaza emzimbeni
- Umbulali wendalo (NK) iiseli – ziphinde zihlasele iiseli zomhlaza, iiseli ezosulelekileyo kwaye zibulale iintsholongwane
Xa i-lymphocytes ifumana utshintsho oluthile lwemfuza, iyahlula kwaye ikhule ngokungalawulekiyo ibangele i-lymphoma. Oku kubangela ukuba amajoni omzimba angakwazi ukubona iiseli ezinomhlaza ezingaqhelekanga okanye angakwazi ukuzitshabalalisa. Iiseli zomhlaza nazo zinokuvelisa iindlela zokuthintela amajoni omzimba ukuba angazihlaseli. Umzekelo, ezinye iiseli zomhlaza zenza iiproteni ezikhethekileyo kumphezulu wazo ezixelela iiseli ze-T ukuba zingazihlaseli.
Unyango ngamachiza kunye nonyango ngemitha ibiziindlela eziqhelekileyo zokunyanga umhlaza. I-Immunotherapy luhlobo lonyango oluphucula ukukwazi komzimba ukubona nokuhlasela iiseli zomhlaza ngokusebenzisa amajoni omzimba.
Yindawo esebenzayo yophando lweklinikhi kwaye kukho unyango oluqinisekisiweyo lwe-immunotherapy. Ezi ziquka i-monoclonal antibody therapy (i-rituximab okanye i-obinutuzumab), ezinye iindlela zonyango ezijoliswe kuzo (umz. I-Pembrolizumab kwi-Hodgkin lymphoma kunye ne-primary mediastinal B-cell lymphoma), kunye kutshanje i-chimeric antigen receptor (CAR) unyango lwe-T-cell.
Yintoni unyango lwe-CAR T-cell?
Unyango lwe-CAR T-cell luhlobo olutsha lwe-immunotherapy esebenzisa i-T-cell yesigulana ukuqaphela kunye nokuhlasela iiseli zomhlaza. Unyango lwe-CAR T-cell lusebenzisa ii-T-cells ezitshintshiweyo ngokuthe ngqo kwaye zijolise ngokuthe ngqo kumhlaza othile, kubandakanywa ezinye ii-subtypes ze-B-cell lymphoma. Iiseli ze-T ezihlaziyiweyo zomeleza amajoni omzimba ukuze ahlasele kwaye abulale iiseli ze-lymphoma.
Iqhezu lee-T-seli zesigulana ziqokelelwa egazini kusetyenziswa inkqubo ebizwa ngokuba yi-apheresis. Ezi seli ziphinde zenziwe ngokutsha kwilabhoratri ekhethekileyo, ngoko ngoku zithwala izakhiwo ezikhethekileyo ezibizwa ngokuba yi-chimeric antigen receptors (CAR) kumphezulu wazo. Ii-CAR ziiprotheyini ezenzelwe ukuba zincamathele kwithagethi ethile kwiiseli zomhlaza. Kwiimveliso ezivunyiweyo ngoku, loo proteni ibizwa ngokuba yi-CD19 efumaneka kumphezulu weeseli ze-B eziqhelekileyo nezinomhlaza.
Iiseli zeCAR T ezenziweyo ziphinda zifakwe kwisigulane (njengotofelo-gazi). Xa bebophelela kwi-receptor yabo ekujoliswe kuyo, baphindaphinda ngokukhawuleza, kwaye babulale iiseli ezijoliswe kuzo kule meko yi-B-cell lymphoma kunye ne-lymphocytes ye-B eqhelekileyo. Ziyaqhubeka ziphindaphindeka kwaye zihlasele iiseli zomhlaza de ziphele zonke.
Kwezinye iimeko, kucatshangelwa ukuba i-CAR T-cells iqhubeka iphila emzimbeni (obizwa ngokuthi "ukuzingisa") kwaye inokuqhubeka nokugcina i-lymphoma okanye i-leukemia. Yiloo nto abantu abaninzi becinga ngee-CAR T-cell 'njengechiza eliphilayo'.
Ngubani ofanelekileyo kunyango lwe-CAR T-cell?
Unyango lwe-CAR T-cell luxhaswa ngemali esidlangalaleni e-Australia kubantu abahlangabezana nemigaqo engqongqo yokufaneleka eya kulandelwa yiphaneli yonyango yengcali. Izigulane eziye zafumanisa ukuba zinesinye sezifo ezidweliswe kwi-B-cell, eziye zabuyela emva ubuncinane ubuncinane be-2 unyango lwangaphambili okanye i-refractory (ayizange iphendule i-chemotherapy) kwaye ifanelekile ngokwezonyango, inokufaneleka kwi-CAR T-cell therapy. Unyango lwe-CAR T-cell lunokuba nemiphumo emibi kakhulu kwaye alufanelekanga kumntu wonke.
Uninzi lwezigulane zidla ngokungena kuxolelo emva kokufumana unyango olusemgangathweni lwangoku lodidi lokuqala oludla ngokuquka ichemotherapy kunye ne-monoclonal antibody. Unyango lwe-CAR T-cell lubiza kakhulu kwaye luxabisa ngaphezulu kwe-500,000 yeedola ngesigulana ngasinye. Iindleko eziphezulu zibangelwa yinkqubo yokuvelisa ingcali ebandakanyekayo ekudaleni ii-CAR T-cell. Kuphela ngamaziko athile omhlaza aya kuqeqeshwa ngokukodwa ukuba afake unyango lwe-CAR T-cell kunye nokulawula ukhathalelo lwezigulane.
Ezi zilandelayo ze-lymphoma subtypes zinokufaneleka:
- Ukusasaza i-B-cell Lymphoma enkulu
- Ukuguqulwa kweFollicular Lymphoma
- IBanga le-3b iFollicular Lymphoma
- I-Primary Mediastinal B-cell Lymphoma
- B-cell Acute Lymphoblastic Lymphoma (B-ALL) ngenxa abantu abangaphantsi kweminyaka engama-26
- Mantle Cell Lymphoma.
Unyango lwe-CAR T-cell e-Australia
E-Australia, kukho iimveliso ezimbini eziye zafumana iingcebiso ezilungileyo ezivela kwiKomiti yeNgcebiso yeeNkonzo zezoNyango (MSAC) kwaye zombini ziya kuxhaswa ngemali esidlangalaleni. Ezi mveliso ziquka:
- IKymriyaTM (tisagenlecleucel) imveliso yeNovartis kwaye ixhaswa ngemali esidlangalaleni eOstreliya
- YescartaTM (axicabtagene ciloleucel) imveliso yaseGiliyadi kwaye ixhaswa ngemali esidlangalaleni eOstreliya
- UTecartusTM (brexucabtagene autoeucel) imveliso yaseGiliyadi exhaswa ngemali esidlangalaleni eOstreliya.
Zonke izibhengezo zixoxwa ziingcali zonyango kwintlanganiso yesizwe yeveki ye-CAR T-cell. Ngolwazi oluthe kratya thetha ne-hematologist yakho okanye iLymphoma Australia.
Ndingalufumana phi unyango lwe-CAR T-cell?
abadala | abantwana |
ENtshona Koloni Isibhedlele sikaFiona Stanley ENew South Wales Isibhedlele iRoyal Prince Alfred Isibhedlele saseWestmead Victoria IZiko loMhlaza kaPeter MacCallum Queensland IRoyal Brisbane kunye neSibhedlele sabaseTyhini | Queensland Isibhedlele saBantwana saseQueensland ENew South Wales Isibhedlele Sabantwana baseSydney Victoria Isibhedlele saBantwana saseRoyal Isibhedlele saseAlfred |
Inkqubo ye-CAR T-cell
Ii-CAR T-cells zenzelwe umntu ngamnye. Unokufumana ezinye iindlela zonyango, ezifana ne-chemotherapy (i-bridging therapy), ukugcina i-lymphoma yakho phantsi kolawulo ngelixa i-CAR T-cells yenziwa (iiveki ze-3-6).
- Ukuqokelelwa kweeseli T: Igazi lithathwa kwisigulana. Iiseli zegazi ezimhlophe, ezibandakanya iiseli ze-T, ziyahlulwa kwaye lonke igazi libuyiselwa kwigazi lesigulana nge-apheresis (efana nokuqokelela iiseli ze-stem). Iiseli ze-T zesigulana zithunyelwa elebhu ukuze zenziwe.
- Ukwenziwa kweeseli ze-CAR T: Iiseli ze-T ziguqulwa okanye zenziwe ngemfuza (zitshintshwe) ukuze zifumane kwaye zibulale iiseli zomhlaza. Iiseli ze-T ezenziwe ngobunjineli ngoku zibizwa ngokuba zii-CAR T-cell. Iiseli zeCAR T zesigulana ziyaphindaphindeka de zibe zizigidi kwaye zibe ngumkhenkce. Ii-CAR T-cell zithunyelwa emva kwisibhedlele sesigulana. Le nkqubo inokuthatha iiveki ezininzi.
- Unyango ngamayeza: Isigulane siya kufumana i-chemotherapy (i-lymphodepletion), ukunciphisa inani leeseli ze-T eziqhelekileyo emzimbeni ukuze zenze indawo ye-CAR T-cell, ukuze zikwazi ukwandisa (ziphindaphinde) xa zilawulwa. Ngokuqhelekileyo, le chemotherapy yi-fludarabine kunye ne-cyclophosphamide.
- I-CAR T-cell infusion: Iiseli zeCAR T zesigulana ziyanyibilika zize ziphinde zibuyiselwe egazini lesigulane, ngokufanayo nokufumana utofelo-gazi okanye iiseli ezisisiqu.
- Emzimbeni wesigulana: Iiseli zeCAR T ziphindaphindeka ngokukhawuleza kwigazi lomguli. I-CAR T-cell ifumana kwaye ibulale iiseli ze-lymphoma. I-CAR T-cells inokuhlala kwigazi ukuze ihlasele ukuba i-lymphoma iyabuya.
- Ukubuyisela: Isigulana siya kubekwa esweni ngononophelo ngexesha nasemva konyango. Izigulane ezifumana unyango lwe-CAR T-cell zinexesha lokubuyisela malunga neenyanga ezi-2-3. Ngeli xesha, izigulane ziya kuvavanywa kwimiphumo emibi kunye nempendulo yonyango. Ubuncinci kwiintsuku ezingama-30 zokuqala emva kokukhutshwa esibhedlele, izigulane kufuneka zihlale kufutshane (kwimizuzu engama-20) kwisibhedlele esinyangayo ukuze zilandelelwe rhoqo okanye zikhathalelwe ngokungxamisekileyo ukuba ziyafuneka.
Imiphumo enokwenzeka ye-CAR T-cell therapy
Onke amayeza kunye nonyango lomhlaza anokubangela iziphumo ebezingalindelekanga. Unyango lwe-CAR T-cell luhlobo olutsha lonyango, kwaye njengoko abaphandi beqonda unyango olungcono, kukwanjalo nokulawulwa kwezi ziphumo ebezingalindelekanga. Unyango lwe-CAR T-cell lunokubangela iziphumo ezibi kakhulu kwaye unyango lunikezelwa kuphela kwizibhedlele kunye namaziko kunye nabasebenzi beengcali ukulawula le miphumo ngokufanelekileyo.
Kubalulekile ukuqaphela ukuba ayizizo zonke izigulana eziya kukwazi ukunyamezela ezinye zeziphumo ebezingalindelekanga kwaye ngoko ke ubume bezonyango kunye nempilo yesigulana ngasinye kufuneka buqwalaselwe ngononophelo phambi kokwenza unyango lwe-CAR T-cell.
Ezinye zeziphumo ebezingalindelekanga eziqhelekileyo zinokuchaphazela uninzi lwezigulane kwaye zinokukhokelela esibhedlele ixesha elide. Ukuphindaphinda kwezi ziphumo bezingalindelekanga kunokudityaniswa nemveliso esetyenzisiweyo, kunye nesigulane kunye nezinto ezinxulumene nesifo. Ezi ziquka:
- Isifo sokukhutshwa kweCytokine
- Umkhuhlane kunye nokubanda
- Uxinzelelo lwegazi oluphantsi kunye namanqanaba aphantsi oksijini
- Iingxaki ze-nervous system kuquka; iingxaki zengqondo (encephalopathy), intloko ebuhlungu, ukuxhuzula okanye ukungcangcazela (ukungcangcazela) okanye isiyezi
- Ukubetha kwentliziyo ngokukhawuleza (tachycardia) kunye notshintsho kwisigqi sentliziyo (arrhythmia)
- Ukudinwa (ukudinwa okugqithisileyo)
- Isiqhamo
- Iimpawu zokugaya ukutya; isicaphucaphu, ukuhlanza, ukunciphisa umdla wokutya, urhudo kunye nokuqunjelwa
- I-Febrile neutropenia (i-neutrophils ephantsi - i-immune system) kunye nezifo
Yintoni i-cytokine release syndrome (CRS)?
I-Cytokine release syndrome (CRS) yimpembelelo enokuthi ibe yingozi kwaye idibene ne-CAR T-cell therapy. I-Cytokines zizithunywa zeekhemikhali ezinceda ii-T-cell zenze imisebenzi yazo, eziveliswa xa iiseli ze-CAR T zanda emzimbeni kwaye zibulala iiseli zomhlaza. Iimpawu ze-CRS zinokusuka kumkhuhlane ombi njengeempawu ukuya kwiimpawu ezimandundu.
Iiseli ze-T zenzelwe ukukhulula i-cytokines (izithunywa zeekhemikhali), ezinceda ukuvuselela kunye nokuqondisa ukuphendula komzimba. Kwimeko ye-CRS, kukho ukukhutshwa okukhawulezayo nokukhulu kwee-cytokines egazini, okunokubangela umkhuhlane ophezulu ngokuyingozi kunye noxinzelelo lwegazi oluphantsi. Oku kukwaziwa ngokuba 'sisivunguvungu se-cytokine'.
Iimpawu ze-cytokine release syndrome
I-CRS idla ngokuvela ngaphakathi kwe-1 ukuya kwiintsuku ze-5 emva kokuba iiseli ze-CAR T zifakwe kwakhona kwisigulane, nangona inokuthi yenzeke kwiiveki kamva kwezinye iimeko. Kwizigulane ezininzi, imeko ithambile ngokwaneleyo ukuba inokulawulwa ngonyango oluxhasayo kunye nokubeka iliso.
Iimpawu kunye neempawu zingabandakanya:
- Fever
- Ukukhathala
- Ukuphelelwa kwesidlo
- Intlungu kunye kunye
- Isihlunu kunye nokuhlanza
- Uhudo
- Rashes
- Ukuphefumla ngokukhawuleza
- Iqondo lentliziyo ekhawulezayo
- Uxinzelelo lwegazi oluphantsi
- Ukuxhamla
- intloko ebuhlungu
- Ukudideka okanye i-delirium
- Hallucinations
- Ukugubha
- Ukuphulukana nokulungelelanisa
Unyango lwe-cytokine release syndrome
Kwizigulane ezininzi, i-CRS inokulawulwa ngonyango oluqhelekileyo oluxhasayo olufana ne-steroids okanye i-intravenous fluids. Njengoko abaphandi baye bazuza amava amaninzi ngonyango lwe-CAR T-cell, bafunda indlela yokulawula ngcono iimeko ezinzulu ze-CRS.
Unyango oluqhelekileyo lwezigulana ukulawula i-CRS enobuzaza kukwenza ichiza elibizwa ngokuba yi-tocilizumab (Actemra).TM). Eli lichiza elaziwa ngaphambili ukunyanga ezinye iimeko zokudumba, ezisetyenziselwa ukuvala i-cytokine ebizwa ngokuba yi-IL-6. I-IL-6 i-cytokine efihliweyo kumanqanaba aphezulu ngamaseli e-T ekuphenduleni ukuvuvukala.
Ezinye izigulane kufuneka zamkelwe ngenxa yolawulo lweziphumo ebezingalindelekanga kwaye zingahlala esibhedlele iveki okanye ngaphezulu. Ezinye izigulane kufuneka zamkelwe ukuze zifumane inkxaso eyongezelelweyo kwiyunithi yokhathalelo olumandla (ICU).
Iingxaki ze-nervous system
Abantu abaninzi abanyangwa ngonyango lwe-CAR T-cell banokufumana iingxaki zenkqubo ye-nervous kwiintsuku ezimbalwa zonyango, nangona iingxaki zinokukhula ukuya kwiiveki ezisi-8 emva konyango. Iingxaki zesixokelelwano semithambo-luvo zikholisa ukuba buthathaka kwaye zibangcono kwiiveki ezimbalwa.
Ezona ngxaki zixhaphakileyo eziphuhlayo zinokuchaphazela indlela esebenza ngayo ingqondo yakho, apho iimpawu zinokuquka ukungcangcazela, intloko ebuhlungu, ukubhideka, ukulahlekelwa ngumlinganiselo, ukuthetha ingxaki, ukuxhuzula kwaye ngamanye amaxesha ukubona izinto ezingekhoyo. Ezi ziphumo bezingalindelekanga zidla ngokuphela emva kweentsuku ezimbalwa, nangona kwezinye zinokuhlala iiveki.
Ukubuyiselwa konyango lwe-CAR T-cell
Ukuchacha kunokuthabatha ixesha njengoko inkqubo yomzimba yokuzikhusela yesigulana ichacha. Ixesha lokubuyisela ngokukhawuleza kunye nokubeka iliso elisondeleyo ngokuqhelekileyo iintsuku ezingama-30 emva kokungena kwe-CAR T-cell. Ngeli xesha izigulane kufuneka zihlale kwisithuba semizuzu engama-20 kwiziko lokunyanga umhlaza. Kufuneka kwakhona babe nomkhathaleli kunye nabo ngawo onke amaxesha ukujonga iimpawu zomkhuhlane, usulelo kunye nobunzima be-neurologic. Uninzi lwezigulana ziziva zidiniwe kwaye azinawo umdla wokutya ngeli xesha.
Iziphumo ebezingalindelekanga zenkqubo yamajoni omzimba
Njengoko unyango lwe-CAR T-cell luchaphazela amajoni akho omzimba, unokuba semngciphekweni omkhulu wosulelo, kubandakanywa usulelo olumandundu emva konyango. Iiseli zakho ezimhlophe zegazi zinokuba sezantsi, kwaye abanye abantu banamanqanaba asezantsi kakhulu e-B-cell kunye namanqanaba asezantsi e-antibody (i-antibodies ziiproteni eziveliswa zii-B-cell ukukunceda ukulwa usulelo). Ezi ngxaki zinokwenza kube nzima kumzimba wakho ukulwa nosulelo. Usenokunikwa amayeza okuthintela usulelo. Ukuba unamanqanaba asezantsi e-antibody, unokufuna unyango lokubuyisela i-immunoglobulin (ukufakwa kwezilwa-buhlungu) ukunceda ukomeleza amajoni akho omzimba.
Ulingo lwezonyango e-Australia
Zininzi iimvavanyo zeklinikhi eziqhutywa ngoku kwihlabathi jikelele ngenani lee-cancer zegazi ezahlukeneyo kunye nomhlaza wethumba eliqinileyo. Kuye kwaboniswa ukuba yimpumelelo kakhulu kwi-B-cell lymphomas ethile. Kukho ngoku amalingo ekliniki e-B-cell lymphoma kulo lonke elase-Australia akhoyo (ukusuka kunyango lodidi lokuqala) ukwenzela:
- Ukusasaza i-B-cell lymphoma enkulu
- Ifollicular lymphoma
- Ingubo yeeseli lymphoma
- I-B-cell non-Hodgkin lymphoma
- I-Lymphocytic leukemia engapheliyo
Ukufumana ulwazi oluthe kratya jonga 'Ukuqonda iiMvavanyo zoNyango' okanye ubone www.iklinity.gov
Ulingo lwezonyango lwamazwe ngamazwe
Maninzi amalingo onyango onyango lwe-CAR T-cell kwihlabathi jikelele. Amazwe aphambili kuphuhliso kunye nolingo lwezonyango afumaneka e-USA naseYurophu. Kukho iimvavanyo zeklinikhi ezijonge kwii-lymphomas ezininzi ezahlukeneyo kunye ne-leukemias ukusuka kunyango lwangaphambili, kwaye kwimeko ebuyeleyo okanye echasayo.
Izilingo zeklinikhi ze-CAR T-cell therapy kubantu zaqala ngo-2012. Yavunywa kuphela yi-FDA (Ukutya kunye noLawulo lweDrug e-USA) kwi-2017 ethe yabona inkqubela ekhawulezayo yehlabathi ekusebenziseni unyango lwe-CAR T-cell.
Abaphandi basazama ukuqonda indlela olu nyango lusebenza ngayo, ukuphucula iziphumo ebezingalindelekanga kunye nokuphucula iziphumo zezigulane. Yindawo ephuhla ngokukhawuleza yophando kwaye inika umdla ukuba ikude kangakanani na ngexesha elifutshane.
Ukufumana ulwazi oluthe kratya jonga 'Ukuqonda iiMvavanyo zoNyango' okanye ubone www.iklinity.gov
Ngolwazi oluthe kratya
- Thetha ne-hematologist yakho malunga nokuba ufanelekile na okanye ufanelekile ukuba ufumane unyango lwe-CAR T-cell. Ukuba kunjalo, ugqirha wakho wegazi unokulungiselela ukuba uthunyelwe.
- Kuyo nayiphi na imibuzo enxulumene nokufaneleka kwesigulana kunyango lwe-CAR T-cell okanye ukuba izigulana zinokufikelela njani kolu nyango, nceda uthumele i-imeyile: CAR-T.enquiry@petermac.org
- Ungaqhagamshelana ne-Lymphoma Nurse Support Line: T 1800 953 081 okanye i-imeyile: nurse@lymphoma.org.au ngolwazi oluthe vetshe okanye iingcebiso.
Iintetho ezirekhodiweyo, udliwano-ndlebe lweengcali kunye nezibonelelo
Uhlaziyo lwe-CAR T-cell Therapy e-Australia-iSeshini yezeMfundo ebibanjwe nge-21 kaNovemba ngo-2020
UGqr Michael Dickinson, iZiko loMhlaza likaPeter MacCallum
Iinoveli zonyango kwi-lymphoma enobundlobongela kunye ne-CAR T-cell therapy
UGqr Michael Dickinson, iZiko loMhlaza likaPeter MacCallum
Unyango lwe-CAR T-cell kunye nokuba luthetha ntoni kwizigulana
Intsebenziswano yiLymphoma Coalition kunye ne-Acute Leukemia Advocates Network- 30th June 2022
I-American Society of Hematology (ASH) udliwano-ndlebe lweengcali
Udliwano-ndlebe lweengcali ze-European Hematology Association
Incwadi ye-CAR T-cell comic - CLL Society
Eminye imibuzo onokuyibuza ugqirha wakho
Ngaba ndifanelekile kunyango lwe-CAR T-cell?
Ngaba lukhona ulingo lwezonyango lwe-CAR T-cell olukhoyo eOstreliya endinokuthi ndilufanelekele?
Ingaba lukhona olunye unyango olungcono kum?
Ngaba lukhona olunye ulingo lwezonyango olukhoyo kum?
Eli phepha ligqityelwe ukuhlaziywa ngo-Agasti 2020
Isigulane kunye nesikhokelo sosapho kwi-CAR T-cell therapy - Amava esigulane
Le vidiyo ingezantsi "Isigulana kunye nesikhokelo sosapho kwi-CAR T-cell therapy" yaphuhliswa ngurhulumente weNSW. Ngenxa yeesethingi zabo zabucala asinakukwazi ukuyidlala kwiphepha lethu lewebhu, kodwa ukuba uyayidlala cofa iqhosha elizuba”Bukela kwiVimeo" ungafikelela kule vidiyo simahla.
