Ucwaningo Lokuphepha Nokusebenza Kahle lwe-Anti-B7-H3 CAR-T Cell Therapy for Recurrent Glioblastoma

March 2023:

Uhlobo lokufunda : Ukungenelela (Isivivinyo Somtholampilo)
Ukubhaliswa Okulinganiselwe : Abahlanganyeli abangu-30
Isabelo: N/A
Imodeli Yokungenela: Ukunikezwa Okulandelanayo
Incazelo Yemodeli Yokungenela: idizayini ethi “3+3” isetshenziselwa ukunquma I-Maximum Tolerated Dose (MTD) kanye nomthamo onconywayo wesigaba sesi-2 (RP2D)
Ukufihla: Akukho (Vula ilebula)
Inhloso Eyinhloko: Ukwelashwa
Isihloko Esisemthethweni: Ucwaningo Oluvuliwe, Ngengalo Eyodwa, Isigaba 1 Sokuhlola Ukuphepha/Ukuphumelela Kokuqala kanye Nokunquma Umthamo Ophakeme Obekezeleleke We-B7-H3-Targeting CAR-T Cell Therapy Ekwelapheni I-Glioblastomas Ephindaphindiwe
Idethi yangempela yokuqala yokufunda : Januwari 27, 2022
Idethi Yokuqeda Okuyisisekelo Elinganiselwe : Disemba 31, 2024
Usuku Olulinganiselwe Lokuphothula : Disemba 31, 2024

Isigaba sokwenyuka komthamo:

Idizayini yokwenyuka komthamo othi “3+3” isetshenziselwa ukunquma i-MTD ne-R2PD. I-Anti-B7-H3 i-autologous Amaseli e-CAR-T zazinikezwa kabili ngeviki ezigulini imithamo elandelayo yomjikelezo ngamunye, nemijikelezo emi-4 njengesifundo esisodwa. Umthamo 1: Iziguli ezi-3 ngethamo lezigidi ezingama-20 amaseli ngomjikelezo ngamunye. Umthamo 2: Iziguli ezi-3 ngethamo lezigidi ezingama-60 amaseli ngomjikelezo ngamunye. Umthamo 3: Iziguli ezi-3 ngethamo lezigidi ezingama-150 amaseli ngomjikelezo ngamunye. Umthamo 4: Iziguli ezi-3 ngethamo lezigidi ezingama-450 amaseli ngomjikelezo ngamunye. Umthamo 5: Iziguli ezi-3 ngethamo lezigidi ezingama-900 amaseli ngomjikelezo ngamunye.

Isigaba sokuqinisekisa i-R2PD:

Nquma i-R2PD ngokusekelwe emiphumeleni yocwaningo lwangaphambilini lokwenyuka komthamo; Yelapha ezinye iziguli eziyi-12 nge-anti-B7-H3 autologous Amaseli e-CAR-T njalo ngeviki ku-R2PD ukuze kuqinisekiswe ukuphepha kwe-R2PD.

Esigabeni ngasinye somthamo, uma iziguli zibonisa ukubekezelelana nokusabela ku- ukwelashwa, lezi ziguli zazizothola izifundo eziningana ze ukwelashwa ngokubona kwe-PI.

Imigomo

Izindlela zokufaka

1. Owesilisa noma owesifazane, oneminyaka eyi-18-75 (kuhlanganise neminyaka eyi-18 nengama-75 ubudala)
2. Iziguli ezine-glioblastoma ebuyele emuva, njengoba kuqinisekiswe i-positron emission tomography (PET) noma i-histological pathology
3. A >= 30% staining extent of B7-H3 in his/her primary/recurrent isisu tissue by the immunochemical method;
4. Isilinganiso sesikali se-Karnofsky >=50
5. Ukutholakala ekuqoqeni i-peripheral blood mononuclear cells (PBMCs)
6. Amanani anele aselabhorethri kanye nokusebenza kwezitho ezanele;
7. Iziguli ezinamandla okuzala/ukuba ngubaba kufanele zivume ukusebenzisa ukuvimbela inzalo okuphumelelayo kakhulu.

Izindlela zokukhishwa

1. Abesifazane abakhulelwe noma abancelisayo
2. Contraindication to bevacizumab
3. Zingakapheli izinsuku ezi-5 ngaphambi kokumnika kweseli ye-CAR-T, abantu abathola ukuphathwa kwe-steroids okuhlelekile ngomthamo omkhulu kuno-10mg/d we-prednisone noma imithamo elinganayo yezinye i-steroids (ngaphandle kwe-corticosteroid ehogeliwe)
4. I-Comorbid nezinye izifo ezimbi ezingalawuleki
5. I-Active immunodeficiency virus (HIV), igciwane le-hepatitis B, igciwane le-hepatitis C noma isifo sofuba;
6. Subjects receiving the placement of a i-carmustine slow-release wafer within 6 months before the enrollment;
7. Izifo ze-Autoimmune;
8. Ukuthola ukwelashwa kwe-immunosuppressive yesikhathi eside ngemuva kokufakelwa kwesitho;
9. Izifo zengqondo ezinzima noma ezingalawuliwe noma isimo esingase sandise izehlakalo ezimbi noma siphazamise ukuhlolwa kwemiphumela;
10. Ayitholakali ebuthi noma imiphumela engemihle ngokwelashwa kwangaphambilini;
11. Izihloko ezibambe iqhaza kolunye ucwaningo lokungenelela phakathi nenyanga eyodwa ngaphambi kokubhaliswa, noma ezithole ezinye izindlela zokwelapha zamaseli e-CAR-T noma ukwelashwa kweseli okushintshiwe ngofuzo ngaphambi kokubhaliswa.
12. Izihloko ezinezimo zezokwelapha ezithinta ukusayina imvume ebhaliwe enolwazi noma ukuthobela izinqubo zocwaningo, okuhlanganisa, kodwa kungagcini nje, izifo zemithambo yenhliziyo, ukungasebenzi kahle kwe-renal/ukwehluleka, i-pulmonary embolism, ukuphazamiseka kokuhlangana, ukutheleleka kwesistimu okusebenzayo, ukutheleleka okungalawuleki, njll. . al., noma iziguli ezingazimisele noma ezingakwazi ukuthobela izinqubo zocwaningo;
13. Izihloko ezinezinye izimo ezingaphazamisa ukubamba iqhaza kwecala ngokubona komseshi.