Ntawm nplooj ntawv no peb yuav tham txog chimeric antigen receptor (CAR) T-cell therapy.
Txheej txheem cej luam
Nkag siab txog CAR T-cell therapy hauv lymphoma
Dr Michael Dickinson, Peter MacCallum Cancer Center
Chimeric antigen receptor (CAR) T-cell therapy yog ib hom kev tiv thaiv kab mob uas siv tib neeg lub cev tiv thaiv kab mob los sim ua kom cov qog ntshav qog ntshav.
Lub cev tiv thaiv kab mob ib txwm tiv thaiv peb thiab yog lub cev tiv thaiv kab mob thiab kab mob, nrog rau mob qog noj ntshav. Nws yog tsim los ntawm lub network ntawm cov kabmob thiab cov qe ntshav dawb tshwj xeeb hu ua lymphocytes. Muaj peb hom lymphocytes uas suav nrog:
- B lymphocytes (B-cells) - uas ua rau cov tshuaj tiv thaiv kab mob sib kis
- T lymphocytes (T-cells) - pab B-hlwb los ua cov tshuaj tiv thaiv kab mob txhawm rau txheeb xyuas cov kab mob, tua kab mob & ncaj qha tua cov kab mob lossis cov qog nqaij hlav hauv lub cev
- Natural killer (NK) hlwb – kuj tua cov qog nqaij hlav cancer, cov kab mob thiab tua cov kab mob
Thaum lymphocytes tau txais qee yam kev hloov pauv caj ces, lawv faib thiab loj hlob tsis tuaj yeem ua rau lymphoma. Qhov no ua rau lub cev tiv thaiv kab mob tsis tuaj yeem kuaj pom cov qog nqaij hlav txawv txav lossis tsis tuaj yeem rhuav tshem lawv. Cov qog nqaij hlav cancer kuj tuaj yeem tsim txoj hauv kev los tiv thaiv lub cev tiv thaiv kab mob los ntawm kev tawm tsam lawv. Piv txwv li, qee cov qog nqaij hlav cancer ua cov protein tshwj xeeb ntawm lawv qhov chaw uas qhia T-hlwb tsis txhob tua lawv.
Cov kws khomob thiab kev kho hluav taws xob tau yog txoj hauv kev los kho mob qog noj ntshav. Immunotherapy yog ib hom kev kho mob uas txhim kho lub cev lub peev xwm los kuaj thiab tua cov qog nqaij hlav cancer los ntawm kev siv lub cev tiv thaiv kab mob.
Nws yog thaj chaw nquag ntawm kev tshawb fawb soj ntsuam thiab muaj pov thawj kev kho mob immunotherapy. Cov no suav nrog kev kho monoclonal antibody (rituximab lossis obinutuzumab), lwm yam kev kho mob (xws li Pembrolizumab hauv Hodgkin lymphoma thiab thawj mediastinal B-cell lymphoma), thiab feem ntau tsis ntev los no chimeric antigen receptor (CAR) T-cell therapy.
CAR T-cell therapy yog dab tsi?
CAR T-cell therapy yog ib yam tshiab ntawm immunotherapy uas siv tus neeg mob tus kheej T-cells kom paub thiab tua cov qog nqaij hlav cancer. CAR T-cell therapy siv tshwj xeeb hloov T-cells ncaj qha thiab ncaj qha rau qee yam qog nqaij hlav, suav nrog qee hom kab mob B-cell lymphoma. Cov reprogrammed T-cells ntxiv dag zog rau lub cev tiv thaiv kab mob los tua thiab tua cov lymphoma hlwb.
Ib feem ntawm tus neeg mob tus kheej T-hlwb yog sau los ntawm cov ntshav siv tus txheej txheem hu ua apheresis. Cov hlwb no tau rov tsim kho dua tshiab hauv chav kuaj tshwj xeeb, yog li tam sim no lawv nqa cov qauv tshwj xeeb hu ua chimeric antigen receptors (CAR) ntawm lawv qhov chaw. CARs yog cov proteins uas tsim los txuas rau lub hom phiaj tshwj xeeb ntawm cov qog nqaij hlav cancer. Rau cov khoom lag luam pom zoo tam sim no, cov protein no hu ua CD19 uas pom nyob rau saum npoo ntawm cov kab mob B-cells ib txwm muaj.
Cov khoom tsim CAR T-cells yog tom qab ntawd rov ua rau tus neeg mob (xws li kev hloov ntshav). Thaum lawv khi rau lawv lub hom phiaj receptor, lawv nce nrawm, thiab tua cov phiaj hlwb uas nyob rau hauv cov ntaub ntawv no yog B-cell lymphoma thiab ib txwm B lymphocytes. Lawv txuas ntxiv mus ntxiv thiab tua cov qog nqaij hlav cancer kom txog thaum lawv tag nrho ploj mus.
Qee zaum, nws tau xav tias CAR T-cells mus nyob hauv lub cev (hu ua "persistence") thiab tuaj yeem ua rau cov qog ntshav qog ntshav lossis qog ntshav nyob rau hauv bay. Qhov no yog vim li cas ntau tus xav tias CAR T-cells yog 'cov tshuaj nyob'.
Leej twg yog tus tsim nyog rau CAR T-cell therapy?
CAR T-cell therapy yog nyiaj txiag rau pej xeem hauv Australia rau cov neeg uas ua tau raws li cov kev cai nruj uas yuav tau ua raws li cov kws kho mob. Cov neeg mob uas tau kuaj pom tias muaj ib qho ntawm cov kab mob B-cell, uas tau rov qab los tom qab tsawg kawg 2 qhov kev kho mob ua ntej los yog refractory (tsis tau teb rau cov kws khomob) thiab kho tau zoo, tuaj yeem tsim nyog rau CAR T-cell therapy. CAR T-cell therapy tuaj yeem muaj kev phiv loj heev thiab tsis haum rau txhua tus.
Feem ntau ntawm cov neeg mob feem ntau nkag mus rau hauv kev zam txim tom qab tau txais kev kho tus qauv thawj kab tam sim no uas feem ntau suav nrog kev kho tshuaj khomob thiab monoclonal antibody. CAR T-cell therapy yog kim heev thiab raug nqi tshaj $500,000 rau ib tus neeg mob. Tus nqi siab yog vim cov txheej txheem tsim khoom tshwj xeeb uas koom nrog tsim CAR T-cells. Tsuas yog qee lub chaw kho mob qog noj ntshav yuav raug cob qhia tshwj xeeb los kho CAR T-cell therapy thiab tswj cov neeg mob.
Cov lymphoma subtypes hauv qab no tuaj yeem tsim nyog:
- Diffuse Loj B-cell Lymphoma
- Hloov pauv Follicular Lymphoma
- Qib 3b Follicular Lymphoma
- Primary Mediastinal B-cell Lymphoma
- B-cell Acute Lymphoblastic Lymphoma (B-ALL) rau cov neeg hnub nyoog qis dua 26
- Mantle Cell Lymphoma.
CAR T-cell therapy hauv Australia
Hauv tebchaws Australia, muaj ob yam khoom uas tau pom zoo los ntawm Pawg Neeg Saib Xyuas Kev Kho Mob (MSAC) thiab yuav tau txais nyiaj sai sai rau pej xeem. Cov khoom no muaj xws li:
- kymriah uaTM (tisagenlecleucel) yog cov khoom lag luam Novartis thiab tau tshaj tawm nyiaj txiag hauv Australia
- YescartaTM (axicabtagene ciloleucel) yog cov khoom lag luam Gilead thiab tau tshaj tawm nyiaj txiag hauv Australia
- TecartusTM (brexucabtagene autoeucel) ib qho khoom lag luam Gilead uas tau tshaj tawm nyiaj txiag hauv Australia.
Txhua qhov kev xa mus yog tham los ntawm cov kws kho mob ntawm lub rooj sib tham hauv lub tebchaws CAR T-cell. Yog xav paub ntxiv tham nrog koj tus kws kho mob hematologist lossis Lymphoma Australia.
Kuv tuaj yeem tau CAR T-cell kho qhov twg?
Cov neeg laus | Cov me nyuam |
Western Australia Fiona Stanley Tsev Kho Mob Tshiab Sab Qab Teb Wales Royal Prince Alfred Tsev Kho Mob Westmead Tsev Kho Mob Victoria Peter MacCallum Cancer Center Queensland Royal Brisbane thiab Women's Hospital | Queensland Queensland Children's Hospital Tshiab Sab Qab Teb Wales Sydney Tsev Kho Mob Me Nyuam Victoria Royal Tsev Kho Mob Cov Menyuam Lub Alfred Hopital |
CAR T-cell txheej txheem
CAR T-cells yog tsim los ntawm tus kheej rau txhua tus neeg. Koj tuaj yeem tau txais lwm yam kev kho mob, xws li tshuaj tua kab mob (txhim kho kev kho mob), kom koj cov qog ntshav qab zib tswj tau thaum lub CAR T-cells raug tsim (3-6 lub lis piam).
- T-cell collection: Ntshav muab los ntawm tus neeg mob. Cov qe ntshav dawb, uas suav nrog T-hlwb, tau muab cais tawm thiab cov ntshav tas li muab rov qab rau hauv tus neeg mob cov hlab ntsha ntawm apheresis (zoo ib yam li khaws cov qia hlwb). Tus neeg mob lub T-cells raug xa mus rau lub chaw kuaj mob rau kev tsim khoom.
- Kev tsim cov CAR T-cells: T-cells raug hloov kho lossis hloov kho (hloov) kom lawv tuaj yeem nrhiav thiab tua cov qog nqaij hlav cancer. Cov engineered T-cells tam sim no hu ua CAR T-cells. Tus neeg mob lub CAR T-cells tau muab ntau ntxiv kom txog thaum muaj ntau lab tus ntawm lawv thiab tom qab ntawd khov. CAR T-cells raug xa rov qab mus rau tus neeg mob lub tsev kho mob. Cov txheej txheem no tuaj yeem siv sijhawm ob peb lub lis piam.
- Kws khomob: Tus neeg mob yuav tau txais chemotherapy (lymphodepletion), txo tus naj npawb ntawm T-cells ib txwm nyob hauv lub cev los ua qhov chaw rau CAR T-cells, yog li lawv tuaj yeem nthuav dav (ntau) ib zaug. Feem ntau, cov tshuaj tua kab mob no yog fludarabine thiab cyclophosphamide.
- CAR T-cell infusion: Tus neeg mob lub CAR T-cells yog thawed thiab muab rov qab rau hauv tus neeg mob cov hlab ntsha, zoo ib yam li tau txais cov ntshav los yog qia hlwb.
- Hauv tus neeg mob lub cev: CAR T-cells sib txuas ceev ceev hauv tus neeg mob cov hlab ntsha. CAR T-cell nrhiav thiab tua cov qog ntshav qog ntshav. CAR T-cells yuav nyob twj ywm hauv cov hlab ntsha los tua yog tias lymphoma rov qab los.
- Rov qab: Tus neeg mob yuav raug saib xyuas kom zoo thaum lub sijhawm thiab tom qab kho. Cov neeg mob uas tau txais kev kho mob CAR T-cell muaj lub sijhawm rov qab los ntawm kwv yees li 2-3 lub hlis. Nyob rau lub sijhawm no, cov neeg mob yuav raug soj ntsuam rau cov kev mob tshwm sim thiab kev kho mob. Lub sijhawm tsawg kawg yog thawj 30 hnub tom qab tso tawm hauv tsev kho mob, cov neeg mob yuav tsum nyob ze (hauv 20 feeb) mus rau lawv lub tsev kho mob kom rov qab saib xyuas tsis tu ncua lossis kev saib xyuas sai yog tias xav tau.
Cov teebmeem tshwm sim ntawm CAR T-cell therapy
Txhua yam tshuaj thiab kev kho mob qog noj ntshav tuaj yeem ua rau muaj kev phiv. CAR T-cell therapy yog ib hom kev kho mob tshiab, thiab raws li cov kws tshawb fawb nkag siab txog kev kho mob zoo dua, yog li kev tswj hwm ntawm cov kev mob tshwm sim no. CAR T-cell therapy tuaj yeem ua rau muaj kev phiv loj heev thiab kev kho mob tsuas yog muab hauv tsev kho mob nrog cov chaw thiab cov neeg ua haujlwm tshwj xeeb los tswj cov kev mob tshwm sim zoo.
Nws yog ib qho tseem ceeb uas yuav tsum nco ntsoov tias tsis yog txhua tus neeg mob yuav muaj peev xwm zam tau qee qhov kev mob tshwm sim thiab yog li txhua tus neeg mob kev kho mob thiab kev noj qab haus huv yuav tsum tau ua tib zoo xav ua ntej ua CAR T-cell kho.
Qee qhov kev mob tshwm sim tuaj yeem cuam tshuam rau feem ntau ntawm cov neeg mob thiab tuaj yeem ua rau mus pw hauv tsev kho mob ntev. Qhov zaus ntawm cov kev mob tshwm sim no tuaj yeem txuas nrog cov khoom siv, thiab rau cov neeg mob thiab cov kab mob cuam tshuam. Cov no suav nrog:
- Cytokine tso tawm mob
- Ua npaws thiab ua daus no
- Ntshav siab thiab qis oxygen
- Cov teeb meem hauv paj hlwb suav nrog; teeb meem ntawm lub hlwb (encephalopathy), mob taub hau, twitching los yog co (tremor) los yog kiv taub hau
- Lub plawv dhia ceev (tachycardia) thiab kev hloov hauv lub plawv dhia (arrhythmia)
- Fatigue (yav dhau heev lawm)
- hnoos
- Cov tsos mob digestive; xeev siab, ntuav, txo qis qab los noj mov, raws plab thiab cem quav
- Febrile neutropenia (tsis tshua muaj neutrophils - lub cev tiv thaiv kab mob) thiab kab mob
cytokine release syndrome (CRS) yog dab tsi?
Cytokine release syndrome (CRS) yog ib qho kev mob tshwm sim loj heev thiab cuam tshuam nrog CAR T-cell therapy. Cytokines yog cov neeg xa xov liaison uas pab cov T-cells ua lawv txoj haujlwm, uas yog tsim thaum CAR T-cells ntau hauv lub cev thiab tua cov qog nqaij hlav cancer. Cov tsos mob CRS tuaj yeem muaj xws li mob khaub thuas me me xws li cov tsos mob mus txog rau cov tsos mob hnyav dua.
T-hlwb yog tsim los tso tawm cytokines (tshuaj xa xov), uas pab txhawb thiab tswj lub cev tiv thaiv kab mob. Nyob rau hauv rooj plaub ntawm CRS, muaj kev tso tawm sai thiab loj ntawm cytokines mus rau hauv cov hlab ntsha, uas tuaj yeem ua rau kub taub hau txaus ntshai thiab txo cov ntshav siab. Qhov no tuaj yeem raug hu ua 'cytokine cua daj cua dub'.
Cov tsos mob ntawm cytokine tso tawm syndrome
CRS zoo li tshwm sim nyob rau hauv 1 mus rau 5 hnub tom qab CAR T-cells rov ua rau tus neeg mob, txawm tias nws yuav tshwm sim ntau lub lis piam tom qab qee kis. Rau cov neeg mob feem ntau, qhov mob me me txaus uas nws tuaj yeem tswj tau nrog kev txhawb nqa kev kho thiab kev saib xyuas.
Cov tsos mob thiab cov tsos mob tuaj yeem suav nrog:
- npaws
- nkees nkees
- Poob tsis qab los noj mov
- Mob thiab pob txha mob
- Xeev thiab ntuav
- Zawv plab
- Rashes
- Ua pa ceev
- Lub plawv dhia ceev ceev
- Tsis tshua muaj ntshav siab
- qaug dab peg
- Mob taub hau
- Tsis meej pem los yog delirium
- hallucinations
- Tremor
- Plam kev sib koom tes
Kev kho mob ntawm cytokine release syndrome
Rau ntau tus neeg mob, CRS tuaj yeem tswj hwm nrog cov qauv kev txhawb nqa xws li steroids lossis cov kua dej tso rau hauv. Raws li cov kws tshawb fawb tau txais kev paub ntau ntxiv nrog CAR T-cell therapy, lawv tab tom kawm yuav ua li cas thiaj tswj tau qhov mob hnyav dua ntawm CRS.
Ib txoj kev kho tus qauv rau cov neeg mob los tswj kev mob hnyav CRS yog los ntawm kev siv tshuaj hu ua tocilizumab (Actemra).TM). Qhov no yog ib yam tshuaj uas twb paub lawm los kho lwm yam mob, uas yog siv los thaiv cov cytokine hu ua IL-6. IL-6 yog ib qho cytokine uas tau zais hauv cov qib siab los ntawm T-hlwb hauv kev teb rau qhov mob.
Qee cov neeg mob yuav tsum tau mus rau kev tswj xyuas cov kev mob tshwm sim thiab tuaj yeem nyob hauv tsev kho mob rau ib lub lis piam lossis yog li ntawd. Qee tus neeg mob yuav tsum tau txais kev txhawb nqa ntxiv hauv chav saib xyuas mob hnyav (ICU).
Teeb meem hauv paj hlwb
Ntau tus neeg kho nrog CAR T-cell therapy tuaj yeem ntsib teeb meem hauv lub paj hlwb hauv ob peb hnub ntawm kev kho mob, txawm hais tias muaj teeb meem tuaj yeem tshwm sim txog 8 lub lis piam tom qab kho. Cov teeb meem hauv paj hlwb feem ntau yog me me thiab zoo dua li ob peb lub lis piam.
Cov teeb meem uas tshwm sim feem ntau tuaj yeem cuam tshuam rau txoj hauv kev uas koj lub hlwb ua haujlwm, qhov twg cov tsos mob yuav muaj xws li tshee, mob taub hau, tsis meej pem, tsis sib npaug, teeb meem hais lus, qaug dab peg thiab qee zaum hnov lus. Cov kev mob tshwm sim no feem ntau txo qis tom qab ob peb hnub, txawm tias qee qhov tuaj yeem nyob ntev li ob peb hnub.
Rov qab los ntawm CAR T-cell therapy
Kev rov qab tuaj yeem siv sijhawm thaum tus neeg mob lub cev tiv thaiv kab mob rov zoo. Lub sijhawm rov qab mob hnyav thiab kev saib xyuas ze yog feem ntau 30 hnub tom qab CAR T-cell infusion. Lub sijhawm no cov neeg mob yuav tsum nyob hauv 20 feeb ntawm qhov chaw kho mob qog noj ntshav. Lawv kuj yuav tsum muaj ib tus neeg saib xyuas nrog lawv txhua lub sijhawm los saib xyuas cov tsos mob ntawm kub taub hau, kab mob thiab teeb meem neurologic. Cov neeg mob feem ntau xav tias nkees thiab tsis qab los noj mov thaum lub sijhawm no.
Immune system phiv
Raws li kev kho mob CAR T-cell cuam tshuam rau koj lub cev tiv thaiv kab mob, tej zaum koj yuav muaj kev pheej hmoo kis mob ntau dua, suav nrog kev kis mob hnyav tom qab kho. Koj cov qe ntshav dawb yuav qis, thiab qee tus neeg muaj cov qib B-cell qis heev thiab cov tshuaj tiv thaiv kab mob qis (antibodies yog cov proteins uas B-hlwb tsim los pab koj tiv thaiv kab mob). Cov teeb meem no tuaj yeem ua rau nws nyuaj rau koj lub cev tiv thaiv kab mob. Tej zaum koj yuav tau txais tshuaj los pab tiv thaiv kab mob. Yog tias koj muaj cov tshuaj tiv thaiv kab mob qis, koj yuav xav tau kev kho tshuaj immunoglobulin hloov pauv (kev txhaj tshuaj tiv thaiv kab mob) los pab txhawb koj lub cev tiv thaiv kab mob.
Kev sim tshuaj hauv Australia
Muaj ntau qhov kev sim tshuaj uas tam sim no tau ua nyob ib ncig ntawm lub ntiaj teb rau ntau hom qog ntshav ntshav thiab qog nqaij hlav qog nqaij hlav. Nws tau pom tias ua tau zoo tshaj plaws hauv qee yam B-cell lymphomas. Tam sim no muaj kev sim tshuaj rau B-cell lymphoma thoob tebchaws Australia muaj (los ntawm kev kho thawj kab) rau:
- Diffuse loj B-cell lymphoma
- Tshwj xeeb ua qog ntshav
- Mantle cell lymphoma
- B-cell non-Hodgkin lymphoma
- Chronic Lymphocytic leukemia
Yog xav paub ntxiv mus saib 'Kev Nkag Siab Txog Kev Kho Mob' lub vev xaib lossis saib www.clinicaltrials.gov
Kev soj ntsuam thoob ntiaj teb
Muaj ntau qhov kev sim tshuaj rau CAR T-cell therapy thoob ntiaj teb. Cov teb chaws loj tshaj plaws hauv kev txhim kho thiab kev sim tshuaj yog nyob hauv Asmeskas thiab Europe. Muaj kev sim tshuaj xyuas ntau yam sib txawv lymphomas thiab leukemias los ntawm kev kho mob pem hauv ntej, thiab hauv qhov chaw rov qab los yog refractory.
Kev sim tshuaj kho mob rau CAR T-cell therapy hauv tib neeg tau pib xyoo 2012. Nws tsuas yog pom zoo los ntawm FDA (Food and Drug Administration in the USA) xyoo 2017 uas txij li tau pom kev nce qib thoob ntiaj teb sai hauv kev siv CAR T-cell therapy.
Cov kws tshawb fawb tseem tab tom sim nkag siab tias qhov kev kho no ua haujlwm li cas, txhim kho cov kev mob tshwm sim thiab txhim kho cov txiaj ntsig rau cov neeg mob. Nws yog ib cheeb tsam loj hlob sai ntawm kev tshawb fawb thiab zoo siab npaum li cas nws tau tuaj nyob rau hauv ib lub sij hawm luv luv.
Yog xav paub ntxiv mus saib 'Kev Nkag Siab Txog Kev Kho Mob' lub vev xaib lossis saib www.clinicaltrials.gov
Yog xav paub ntxiv
- Tham nrog koj tus kws kho mob hematologist seb koj puas tsim nyog lossis tsim nyog los kho CAR T-cell. Yog tias muaj, koj tus kws kho mob hematologist tuaj yeem teem caij xa mus.
- Rau ib qho lus nug ntsig txog tus neeg mob tsim nyog tau txais kev kho mob CAR T-cell lossis cov neeg mob tuaj yeem nkag mus rau qhov kev kho no, thov email: CAR-T.enquiry@petermac.org
- Koj tuaj yeem hu rau Lymphoma Nurse Support Line: T 1800 953 081 lossis email: Nurse@lymphoma.org.au yog xav paub ntxiv los yog tswv yim.
Sau cov kev nthuav qhia, kev xam phaj kws tshaj lij thiab cov peev txheej
Kev Hloov Kho ntawm CAR T-cell Therapy hauv Australia - Kev Kawm Txuj Ci tau tuav 21 Kaum Ib Hlis 2020
Dr Michael Dickinson, Peter MacCallum Cancer Center
Kev kho tshiab tshiab hauv kev mob qog ntshav qog ntshav & CAR T-cell therapy
Dr Michael Dickinson, Peter MacCallum Cancer Center
CAR T-cell kev kho mob thiab nws txhais li cas rau cov neeg mob
Kev koom tes los ntawm Lymphoma Coalition thiab Acute Leukemia Advocates Network - 30th Lub Rau Hli 2022
American Society of Hematology (ASH) kev xam phaj kws tshaj lij
European Hematology Association cov kws tshaj lij kev xam phaj
CAR T-cell comic phau ntawv - CLL Society
Qee cov lus nug nug koj tus kws kho mob
Kuv puas tsim nyog rau CAR T-cell therapy?
Puas muaj CAR T-cell therapy kev sim tshuaj muaj nyob hauv Australia uas kuv yuav tsim nyog tau txais?
Puas muaj lwm yam kev kho mob uas zoo dua rau kuv?
Puas muaj lwm yam kev sim tshuaj rau kuv?
Nplooj ntawv no tau hloov kho tshiab kawg Lub Yim Hli 2020
Tus neeg mob thiab tsev neeg qhia rau CAR T-cell therapy - Tus neeg mob kev paub
Cov video hauv qab no "Tus neeg mob thiab tsev neeg qhia txog CAR T-cell therapy" tau tsim los ntawm tsoomfwv NSW. Vim lawv qhov chaw ntiag tug peb tsis tuaj yeem ua si hauv peb lub vev xaib, tab sis yog tias koj nyem rau ntawm lub pob xiav "Saib ntawm Vimeo" koj tuaj yeem nkag mus rau qhov video no dawb.
