Ma'aikatan gwaji na asibiti don maganin BALL CAR T-Cell

16th Maris 2023: Maganin ciwon daji ana samun juyi ta hanyar sabbin magungunan rigakafi waɗanda ke kaiwa ga microenvironment a wurin ƙari. Kwayoyin T tare da masu karɓar antigen na chimeric (CAR) ana yin bincike sosai don rigakafin cutar kansa. Tisagenlecleucel, nau'in tantanin halitta na CAR-T na CD19, ya sami amincewar asibiti yanzu. Ana gwada ƙirar CAR da aka yi niyya kan sabbin maƙasudai waɗanda ke da alaƙa da cututtukan jini da ƙaƙƙarfan malignancies a ci gaba. gwaji na asibiti. 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.

Ci gaban ƙwayoyin CAR-T suna ci gaba tare da yin amfani da na'urorin CAR-T na duniya da T cell mai karɓa. A cikin wannan binciken, mun yi rajistar gwajin asibiti na ƙwayoyin CAR-T a kasar Sin, mun tantance kaddarorin gine-ginen CAR, kuma mun ba da taƙaitaccen bayani game da yanayin nazarin CAR-T a Sin.

Yanayin yanayin CAR T-Cell far a China ya yi girma cikin sauri a cikin 'yan shekarun da suka gabata. daukar ma'aikata don CAR T-Cell gwajin gwaji na asibiti Ana ci gaba da gudana a wasu manyan cibiyoyin ciwon daji a kasar Sin. An jera wasu daga cikin cibiyoyi a kasar Sin wadanda ke gudanar da wadannan gwaje-gwajen asibiti:

1. Asibitin Hematology na Tianjin (Legend Bio)
2. Asibitin Lardin Anhui (Cells: Bioheng)
3. Asibitin Jami'ar Peking, Shenzhen (Cells: Bioheng)
4. Asibitin haɗin gwiwa na 1st na Jami'ar Soochow (Unicar-Therapy)
5. Asibitin Xiangya na 3 na Jami'ar Kudu ta Tsakiya (Unicar-Therapy)

Tsangwama / Jiyya: CD19-Niyya Chimeric Antigen Recetor (CAR) T Kwayoyin

Cikakken bayanin:

Binciken kashi na wannan binciken zai zama ƙirar 3+3 tare da ƙimar DLT da aka yi niyya na <1/3. Za'a iya dakatar da binciken kashi sau ɗaya ko fiye da matakan kashi tare da ingantaccen bayanin martaba kuma an zaɓi ingantaccen aikin antitumor don kimantawa na gaba. Matsakaicin adadin haƙuri (MTD) ƙila ba za a samu ba a matakan kashi da aka ƙaddara a cikin wannan binciken, kamar yadda aka bayyana a ƙasa.

A lokacin lokacin jiyya na binciken, za a kimanta matakan kashi huɗu na JWCAR029. rajista za a fara a matakin kashi na 1, bi ka'idar ƙirar bincike na kashi 3 + 3, kuma a ƙarshe zaɓi matakan kashi ɗaya ko fiye tare da ingantaccen bayanin martaba da ingantaccen aikin antitumor a matsayin adadin da aka ba da shawarar, bayan haka za a dakatar da binciken kashi.

Za a kimanta ƙayyadaddun ƙayyadaddun ƙwayar cuta (DLT) a cikin kwanaki 28 bayan jiko na JWCAR029. An shirya kowace ƙungiya ta kashi don yin rajistar batutuwa uku da farko, kuma aƙalla batun likitancin yara da ke ƙasa da shekaru 10 wanda za a iya kimantawa don DLT za a yi rajista a kowane matakin kashi. A cikin rukunin kashi na farko, batutuwa 3 na farko za a cusa aƙalla kwanaki 14. A kowane matakin kashi mafi girma, marasa lafiya 3 na farko a cikin rukunin kashi za a kula da su aƙalla kwanaki 7. Don matakan kashi da aka yi la'akari da aminci, aƙalla batutuwa 3 tare da DLT mai ƙima dole ne su cika lokacin tantancewar DLT na kwanaki 28.

Ka'idodin Hadawa:

1. Shekaru ≤ 30 shekaru da nauyi ≥10kg.
2. Marasa lafiya tare da r / r B-ALL, wanda aka ayyana azaman cututtukan ƙwayar cuta a cikin kasusuwan kasusuwa (≥5% fashewa) da ɗayan waɗannan masu zuwa:
   • ≥2 BM koma baya;
   • Refractory da aka ayyana azaman koma baya idan farkon gafara <watanni 12 ko rashin samun CR bayan sake zagayowar 1 na daidaitaccen tsarin induction chemotherapy don sake dawo da cutar sankarar bargo; chemo-refractory na farko kamar yadda aka ayyana ta rashin samun CR bayan sake zagayowar 1 na al'ada chemotherapy ko 2 hawan keke na daidaitaccen tsarin induction chemotherapy don cutar sankarar bargo ta koma baya;
   • Duk wani sake dawowar BM bayan HSCT wanda dole ne ya kasance ≥90 kwanaki daga HSCT a lokacin tantancewa, kuma ana buƙatar samun 'yanci daga GVHD kuma ya ƙare daga duk wani maganin rigakafin rigakafi ≥1 wata a lokacin dubawa;
   • Marasa lafiya da ke da Ph+ ALL sun cancanci idan ba su da haƙuri ko kuma sun kasa layukan jiyya na TKI guda biyu, ko kuma idan an hana maganin TKI.
   Lura: Marasa lafiya tare da MRD+ bayan haɗin magani za a ba su izinin magani.
3. Karnofsky (shekaru ≥16 shekaru) ko Lansky (shekaru <16) Matsayin aikin> 60.
4. Isasshen aikin gabobi.
5. Samun damar jijiyoyi ya wadatar don keɓewar leukocyte.
6. Lokacin tsira da ake tsammani> watanni 3.
7. Duk wani cututtukan da ba na jini ba saboda maganin da ya gabata, ban da alopecia da neuropathy na gefe, dole ne a mayar da shi zuwa ≤ 1.
8. Matan da ke da yuwuwar haifuwa (duk batutuwan mata waɗanda ke da ilimin physiologically iya ɗaukar ciki) dole ne su yarda su yi amfani da ingantaccen tsarin hana haifuwa na shekara 1 bayan jiko na JWCAR029; batutuwa maza waɗanda abokan aikinsu ke da yuwuwar haifuwa dole ne su yarda su yi amfani da ingantacciyar hanyar shinge ta hana haifuwa na shekara 1 bayan jiko na JWCAR029.

Ka'idojin keɓewa:

1. Mutanen da ke fama da cutar sankarar bargo a cikin tsarin kulawa na tsakiya (CNS) waɗanda ke da raunin CNS masu aiki da kuma alamun bayyanar cututtuka na neurodegenerative, ko kuma mutanen da CNS ke tsakanin CNS-2 da CNS-3 bisa ga ka'idodin NCCN (mutanen da CNS CNS ke CNS-2 saboda ana iya shigar da raunin huda).
2. Abubuwan da suka wanzu ko na asibiti masu mahimmanci na CNS irin su farfadiya, farfaɗowa, gurgunta, aphasia, edema na kwakwalwa, bugun jini, raunin kwakwalwa mai tsanani, ciwon hauka, cutar Parkinson, cutar cerebellar, ciwon kwakwalwar kwakwalwa, psychosis, da dai sauransu.
3. Marasa lafiya masu ciwon ƙwayar cuta banda Down syndrome.
4. Marasa lafiya tare da Burkitt ta lymphoma.
5. Tarihin malignancy banda B-ALL na aƙalla shekaru 2 kafin yin rajista.
6. Jigon yana da HBV, HCV, HIV ko syphilis kamuwa da cuta a lokacin tantancewa.
7. Abun yana da zurfin jijiya thrombosis (DVT) (cancer thrombosis ko thrombosis) ko huhu artery embolism (PE) ko kuma yana kan maganin rigakafi don DVT ko PE a cikin watanni 3 kafin sanya hannu kan takardar izinin da aka sanar.
8. fungal tsarin da ba a sarrafa shi ba, ƙwayoyin cuta, ƙwayoyin cuta ko wasu cututtuka.
9. Haɗuwa da cututtukan autoimmune masu aiki waɗanda ke buƙatar maganin rigakafi.
10. Cuta mai tsanani ko na kullum.
11. Tarihin kowane ɗayan cututtukan cututtukan zuciya masu zuwa a cikin watanni 6 da suka gabata: Class III ko IV gazawar zuciya kamar yadda New York Heart Association (NYHA) ta ayyana, angioplasty na zuciya ko stenting, ciwon zuciya na zuciya, angina mara tsayayye, ko wasu cututtukan zuciya na asibiti.
12. Mata masu ciki ko masu shayarwa. Mata masu yuwuwar haifuwa dole ne su yi gwajin ciki mara kyau a cikin sa'o'i 48 kafin fara gwajin cutar sankara na lymphocyte.
13. Magani na baya tare da ƙwayoyin CAR-T ko wasu ƙwayoyin halittar T da aka gyara.
14. Maganin anti-CD19/anti-CD3 na baya, ko duk wani maganin CD19 na gaba.
15. Magungunan da suka dace ko jiyya a cikin ƙayyadadden lokaci.
16. kasancewar duk wasu abubuwan da, a ra'ayin mai binciken, na iya yin wahala ko gagara ga wani batu ya bi ƙa'idar, irin su likita, tunani, dangi, ilimin zamantakewa, ko yanayin yanki, da rashin yarda ko rashin iya yin hakan. haka.
17. Sanannun halayen rashin lafiyar da ke barazanar rayuwa, halayen rashin hankali, ko rashin haƙuri ga ƙirar tantanin halitta na JWCAR029 ko abubuwan da ke cikin sa.

Disclaimer

Jerin binciken akan wannan gidan yanar gizon baya nufin cewa hukumomi sun sake duba shi. Amincewa da ingancin kimiyyar binciken da aka jera anan alhakin mai ɗaukar nauyin binciken ne da masu bincike. Sanin kasada da yuwuwar fa'idodin karatun asibiti, kuma kuyi magana da mai ba da lafiyar ku kafin shiga.

Masu daukar nauyin karatu da masu bincike ne ke da alhakin tabbatar da cewa binciken ya bi duk dokoki da ka'idoji da suka dace kuma suna ba da bayanai akan gidan yanar gizon. Ma'aikatan NLM ba sa tabbatar da ingancin kimiyya ko dacewa da bayanan da aka ƙaddamar fiye da ƙayyadaddun kulawar inganci don bayyananniyar kurakurai, rashi, ko rashin daidaituwa.

Zaɓin saka hannu cikin nazari muhimmin yanke shawara ne na kai. Kafin ka shiga cikin binciken, tattauna duk zaɓuɓɓuka tare da mai ba da lafiyar ku da sauran amintattun masu ba da shawara. Don ƙarin bayani game da shiga cikin nazarin asibiti, duba Koyi Game da Nazarin Nazari, wanda ya haɗa da tambayoyin da za ku so ku yi kafin yanke shawarar shiga cikin binciken.