Ukuqashwa kwesilingo somtholampilo sokwelashwa kwe-BALL CAR T-Cell

I-16th Mashi 2023: Ukwelashwa komdlavuza kulungiswa kabusha ngemithi emisha ye-immunotherapeutic eqondise i-microenvironment endaweni yesimila. Amaseli e-T ane-chimeric antigen receptors (CAR) acwaningwa kabanzi nge-immunotherapy yomdlavuza. I-Tisagenlecleucel, uhlobo lweseli ye-CAR-T eqondene ne-CD19, isanda kuthola imvume yomtholampilo. Imiklamo ye-CAR eqondiswe kumanoveli okuhlosiwe ahileleke ezenzweni ze-hematological kanye nezifo eziqinile ziyahlolwa ngokuqhubekayo. izivivinyo zokwelashwa. Simultaneous and sequential CAR-T cells are also being investigated for potential clinical uses, in addition to single-target CAR-T cell experiments. Clinical trials for CAR-engineered T cells with several targets are also starting.

Ukuthuthukiswa kwamaseli e-CAR-T kuqhubekela phambili ngokusetshenziswa kwamaseli e-CAR-T enziwe universal kanye ne-T cell receptor. Kulolu cwaningo, sibhalise izivivinyo zomtholampilo zamaseli e-CAR-T e-China, sahlola izakhiwo ze-CAR, futhi sanikeza umbono omfishane wendawo yocwaningo lwe-CAR-T e-China.

Indawo ye Ukwelashwa kwe-CAR T-Cell eChina ikhule ngesivinini esikhulu eminyakeni embalwa edlule. Ukuqashwa kwe Izivivinyo zomtholampilo zokwelashwa kwe-CAR T-Cell ziyaqhubeka kwezinye zezikhungo ezihamba phambili zomdlavuza eChina. Kufakwe ohlwini ezinye zezikhungo e-China ezenza lezi zivivinyo zomtholampilo:

1. Isibhedlela i-Tianjin Hematology (Legend Bio)
2. Isibhedlela Sesifundazwe sase-Anhui (Amaseli: Bioheng)
3. Peking University Hospital, Shenzhen (Amaseli: Bioheng)
4. Isibhedlela sokuqala Esihlobene Nenyuvesi yaseSoochow (Unicar-Therapy)
5. I-3rd Xiangya Hospital yaseCentral South University (Unicar-Therapy)

Ukungenelela / Ukwelashwa : Okuhloswe ku-CD19 I-Chimeric Antigen Receptor (CAR) T Amaseli

Incazelo enemininingwane:

Ukuhlola umthamo walolu cwaningo kuzoba umklamo ongu-3+3 onenani eliqondiwe le-DLT elingu-<1/3. Ukuhlolwa kwethamo kungayekiswa uma ileveli yomthamo owodwa noma ngaphezulu ngephrofayela eyamukelekayo yokuphepha kanye nomsebenzi owanelisayo wokulwa nesimila usukhethiwe ukuze uhlolwe okulandelayo. Umthamo omkhulu obekezeleleke kakhulu (MTD) ungase ungafinyelelwa emazingeni omthamo anqunywe kusengaphambili kulolu cwaningo, njengoba kuchazwe ngezansi.

Phakathi nesikhathi sokwelashwa socwaningo, amazinga emithamo amane e-JWCAR029 azohlolwa. ukubhaliswa kuzoqala ezingeni le-dose 1, kulandele iphrothokholi yokuklama yokuhlola umthamo we-3+3, futhi ekugcineni ukhethe ileveli yomthamo owodwa noma ngaphezulu enephrofayili yokuphepha eyamukelekayo nomsebenzi omuhle we-antitumors njengomthamo onconyiwe, ngemva kwalokho ukuhlola umthamo kuzoyekiswa.

Ubuthi bokunciphisa umthamo (i-DLT) buzohlolwa phakathi kwezinsuku ezingu-28 ngemva kokumnika kwe-JWCAR029. Iqoqo ngalinye lethamo lihlelelwe ukubhalisa izifundo ezintathu ekuqaleni, futhi okungenani isifundo esisodwa sezingane esingaphansi kweminyaka eyi-10 esingahlolelwa i-DLT sizobhaliswa kuleveli yomthamo ngamunye. Eqenjini lethamo lokuqala, izifundo zokuqala ezi-3 zizofakwa okungenani izinsuku eziyi-14 ngokuhlukana. Kulelo nalelo zinga ledosi ephezulu, iziguli zokuqala ezi-3 phakathi kweqoqo lethamo zizophathwa okungenani izinsuku eziyi-7 ngokuhlukana. Kumazinga omthamo athathwa njengaphephile, okungenani izifundo ezi-3 ezine-DLT ehlolekayo kufanele ziqedele isikhathi sokuhlola se-DLT sezinsuku ezingama-28.

Imigomo Yokufaka:

1. Ubudala ≤ iminyaka engu-30 nesisindo ≥10kg.
2. Iziguli ezine-r/r B-ALL, ezichazwa njengesifo se-morphological emnkantsheni (≥5% ukuqhuma) kanye nokunye kokulandelayo:
   • ≥2 BM kabusha;
   • I-Refractory ichazwa njengokuphindwa kabusha uma ukuxolelwa kokuqala <izinyanga eziyi-12 noma kungafinyeleli i-CR ngemva komjikelezo ongu-1 womuthi ojwayelekile we-chemotherapy wokungeniswa kwe-leukemia ephindekile;i-chemo-refractory eyinhloko njengoba kuchazwe ngokungafinyeleli i-CR ngemva komjikelezo ongu-1 we-chemotherapy evamile noma imijikelezo emi-2 uhlobo olujwayelekile lwe-chemotherapy lokungeniswa kwe-leukemia ebuyele emuva;
   • Noma iyiphi i-BM iphinde ibuye ngemva kwe-HSCT okufanele ibe yizinsuku ezingu-≥90 kusukela ku-HSCT ngesikhathi sokuhlolwa, futhi kudingeke ukuthi ikhululeke ku-GVHD futhi iphele kunoma iyiphi indlela yokwelapha evikela amasosha omzimba ≥1 inyanga ngesikhathi sokuhlolwa;
   • Iziguli ezine-Ph+ ZONKE zifanelekile uma zingabekezeleli noma zehlulekile imigqa emibili yokwelashwa kwe-TKI, noma uma ukwelashwa kwe-TKI kunqatshelwe.
   Qaphela: Iziguli ezine-MRD+ ngemva kokwelashwa kwe-bridging zizovunyelwa ukwelashwa.
3. U-Karnofsky (iminyaka engu-≥16 iminyaka) noma u-Lansky (iminyaka engu-<16 yeminyaka) isimo sokusebenza >60.
4. Ukusebenza kwezitho ezanele.
5. Ukufinyelela kwe-Vascular kwanele ukuhlukaniswa kwe-leukocyte.
6. Isikhathi sokusinda esilindelwe > izinyanga ezi-3.
7. Noma yibuphi ubuthi obungewona owe-hematological ngenxa yokwelashwa kwangaphambilini, ngaphandle kwe-alopecia ne-peripheral neuropathy, kufanele bubuyiselwe ku-≤ grade 1.
8. Abesifazane abanamandla okuzala (bonke abantu besifazane abakwazi ukukhulelwa ngokomzimba) kufanele bavume ukusebenzisa indlela ephumelela kakhulu yokuvimbela inzalo unyaka ongu-1 kulandela ukumnika kwe-JWCAR029; abantu besilisa ophathina babo abanamandla okuzala kufanele bavume ukusebenzisa indlela yokuvimbela inzalo esebenzayo unyaka ongu-1 kulandela ukumnika kwe-JWCAR029.

Imigomo Yokukhishwa:

1. Abantu abane-leukemia ohlelweni lwezinzwa olumaphakathi (CNS) abanezilonda ze-CNS ezisebenzayo kanye nezimpawu ezibalulekile ze-neurodeergenerative, noma abantu abane-CNS grade ephakathi kwe-CNS-2 ne-CNS-3 ngokweziqondiso ze-NCCN (abantu abasigaba sabo se-CNS yi-CNS-2 ngenxa ukulimala kokubhoboza kungase kubhaliswe).
2. Izilonda ezikhona noma zangaphambilini ezibalulekile ze-CNS ezifana nesifo sokuwa, isithuthwane, ukukhubazeka, i-aphasia, i-cerebral edema, unhlangothi, ukulimala okukhulu kobuchopho, ukuwohloka komqondo, isifo sika-Parkinson, isifo sobuchopho, i-organic brain syndrome, i-psychosis, njll.
3. Iziguli ezine-genetic syndromes ngaphandle kwe-Down syndrome.
4. Iziguli ezine I-lymphoma kaBurkitt.
5. Umlando wobubi ngaphandle kwe-B-ALL okungenani iminyaka emi-2 ngaphambi kokubhaliswa.
6. Isihloko sasine-HBV, HCV, HIV noma ugcunsula ngesikhathi sokuhlolwa.
7. Isihloko sine-deep vein thrombosis (DVT) (cancer thrombosis noma thrombosis) noma i-pulmonary artery embolism (PE) noma sisekwelashweni kwe-anticoagulation ye-DVT noma i-PE phakathi nezinyanga ezi-3 ngaphambi kokusayina ifomu lemvume enolwazi.
8. ukutheleleka kwe-systemic fungal, amagciwane, amagciwane noma ezinye izifo ezingalawuleki.
9. Inhlanganisela yezifo ezisebenzayo ze-autoimmune ezidinga ukwelashwa kwe-immunosuppressive.
10. Isifo esibi noma esingamahlalakhona sokuxhunyelelwa ngokumelene ne-host host.
11. Umlando wanoma isiphi kwalezi zifo ezilandelayo zenhliziyo nemithambo yegazi phakathi nezinyanga eziyi-6 ezedlule: Ikilasi III noma IV ukuhluleka kwenhliziyo njengoba kuchazwe yi-New York Heart Association (NYHA), i-angioplasty yenhliziyo noma i-stenting, i-myocardial infarction, i-angina engazinzile, noma esinye isifo senhliziyo esibalulekile emtholampilo.
12. Abesifazane abakhulelwe noma abancelisayo. Abesifazane abasemathubeni okuzala kufanele babe nokuhlolwa kwe-serum yokukhulelwa okungekuhle kungakapheli amahora angama-48 ngaphambi kokuqala kwe-lymphocyte clearance chemotherapy.
13. Ukwelashwa kwangaphambilini ngamaseli e-CAR-T noma amanye amaseli e-T ashintshwe ufuzo.
14. Ukwelashwa kwangaphambilini kwe-anti-CD19/anti-CD3, nanoma yiluphi olunye uhlobo lokwelapha lwe-anti-CD19.
15. Imithi noma imithi yokwelapha efanelekile phakathi nesikhathi esibekiwe.
16. ukuba khona kwanoma yiziphi izici, ngokombono womphenyi, ezingenza kube nzima noma kungenzeki ngesihloko ukulandela umthetho olandelwayo, njengezimo ezingalawuleki zezokwelapha, ezengqondo, zomndeni, zezenhlalo, noma zezwe, kanye nokungafuni noma ukungakwazi ukwenza ngakho.
17. Ukungezwani okwaziwayo okusongela ukuphila, ukuzwela okukhulu, noma ukungabekezelelani ekwakhiweni kwamaseli e-JWCAR029 noma izinto ezisizayo.

Disclaimer

Uhlu locwaningo kule webhusayithi akusho ukuthi iziphathimandla zilubuyekezile. Ukuphepha nokuba semthethweni kwesayensi kocwaningo olufakwe lapha kuwumthwalo womxhasi wocwaningo nabaphenyi. Yazi ubungozi kanye nezinzuzo ezingaba khona zezifundo zomtholampilo, futhi ukhulume nomhlinzeki wakho wokunakekelwa kwezempilo ngaphambi kokuba ubambe iqhaza.

Abaxhasi bocwaningo nabaphenyi yibona abaphethe ukuqinisekisa ukuthi izifundo zithobela yonke imithetho neziqondiso ezifanele futhi zihlinzeka ngolwazi kuwebhusayithi. Izisebenzi ze-NLM azikuqinisekisi ukufaneleka kwesayensi noma ukuhambisana kolwazi oluthunyelwe ngale kokubuyekezwa kokulawulwa kwekhwalithi okulinganiselwe ngamaphutha asobala, ukushiyeka, noma ukungahambisani.

Ukukhetha ukuhlanganyela esifundweni kuyisinqumo somuntu siqu esibalulekile. Ngaphambi kokuba ubambe iqhaza ocwaningweni, xoxa ngazo zonke izindlela ongakhetha kuzo nomhlinzeki wakho wokunakekelwa kwezempilo kanye nabanye abeluleki abathembekile. Ukuze uthole ulwazi olwengeziwe mayelana nokubamba iqhaza ezifundweni zemitholampilo, bheka Funda Ngezifundo Zomtholampilo, ezihlanganisa imibuzo ongase ufune ukuyibuza ngaphambi kokuthatha isinqumo sokubamba iqhaza ocwaningweni.