satricabtagene autoleucel (Satri-cel,CT041)

I-satricabtagene autoleucel (Satri-cel, CT041) yimveliso ye-CAR T-cell ekhethiweyo ngokuchasene neproteni yeClaudin18.2 enokuba yeyokuqala kwihlabathi liphela. I-Satri-cel ijolise kwi-Claudin18.2 solid tumors egxile kakhulu kumhlaza wesisu/umhlaza we-gastroesophageal junction (GC/GEJ) kunye nomhlaza we-pancreatic (PC).

Iziphumo zokugqibela zovavanyo oluqalwe ngumphandi i-CT041-CG4006 (NCT03874897) lwe-satricabtagene autoleucel zipapashwe kwi-Nature Medicine ngoJuni 3, 2024.

Izigulane ezingama-98 zizonke zithathe inxaxheba kolu vavanyo, kwaye iziphumo zibonise ukuba izinga lokulawula isifo (DCR) liphezulu ukuya kuthi ga kwi-91.8%, izigulane ezingama-38 zifumene ukuxolelwa, izinga lokuxolelwa lilonke lalingama-38.8%, i-median progression free survival (PFS) yayiziinyanga ezi-4.4, i-median overalvage survival (OS) yayiziinyanga ezi-8.8, kwaye ixesha eliphakathi lokuxolelwa (mDOR) yayiziinyanga ezi-6.4. Phakathi kwezigulane ezingama-90 ezijoliswe kwi-baseline lesion, izigulane ezingama-70 zifumene amanqanaba ahlukeneyo okuncitshiswa kwe-tumor.

Phakathi kwezigulane ezingama-51 ezinomhlaza wesisu ezinyangwe nge-monotherapy nge-Satri-cel, izinga lokulawula isifo laliphezulu ukuya kuthi ga kwi-96.1% (49), kwaye izinga lokuphendula lilonke lalingama-54.9% (28). Phakathi kwazo, izigulane ezingama-27 zifumene impendulo engaphelelanga (PR), isigulane esinye sifumene impendulo epheleleyo (CR), kwaye ubude bexesha eliphakathi lokuphendula (mDOR) yayiziinyanga eziyi-6.4.

Isiphelo

I-Satri-cel ibonisa amandla okunyanga ngeprofayili yokhuseleko elawulekayo kwizigulane ezine-CLDN18.2-positive advanced gastrointestinal cancer.

Ngomhla wesi-9 kweyoMsintsi ngo-2023, amatyala amabini okunyanga umhlaza wepancreatic osasazekayo nge-CARsgen's CT041, iClaudin (CLDN) 18.2 CAR T-cell Therapy entsha, apapashwe kwiJournal of Hematology & Oncology enesihloko esithi “CT041 CAR T cell therapy for Claudin18.2 positive metastatic pancreatic cancer”.

Kwimeko yoku-1, umfazi oneminyaka engama-58 ubudala wafunyaniswa enomhlaza wepancreatic one-metastasis yamaphaphu kunye nama-lymph nodes. I-nab-paclitaxel yomgca wokuqala kunye ne-gemcitabine kunye ne-irinotecan-liposome yomgca wesibini kunye ne-5-flurouracil aziphumelelanga ngaphambi kokuba abhaliswe kuvavanyo lweklinikhi lwe-CT041, emva kokuqinisekisa ukubonakaliswa kwe-CLDN18.2 njenge-2+/70%. Emva kwe-lymphodepletion equka i-fludarabine, i-cyclophosphamide, kunye ne-nab-paclitaxel, idosi ye-CT041 ye-250 × 10⁶iiseli zanikwa isigulana ngoSeptemba 2021. I-Grade 2 cytokine release syndrome (CRS) yenzeka, eyathi kamva yalawulwa yi-tocilizumab. Impendulo engaphelelanga (PR) yafezekiswa ngokwe-RECIST v1.1, kunye nokuncipha okukhulu kwe-metastasis yemiphunga.

Kwimeko yesi-2, umfazi oneminyaka engama-75 ubudala wafunyaniswa ukuba unomhlaza we-pancreas we-pT2N0 emva kokuba etyandwe ngoMeyi 2019. Ukwanda kwe-lung metastasis kwafunyanwa emva kweenyanga ezi-5 ngexesha lokulandela emva kotyando. I-S-1 monotherapy yanikwa njenge-chemotherapy yomgca wokuqala ukususela ngoDisemba 2019. Ngexesha lotyando lwe-palliative radiation, ukuqhubela phambili kwe-tumor kwabonwa kwimiphunga. Ekubeni ukubonakaliswa kwe-CLDN18.2 kwafunyaniswa njenge-3+/60%, isigulana sabhaliswa kwisilingo seklinikhi se-CT041. Emva kokufumana i-lymphodepletion equka i-fludarabine, i-cyclophosphamide kunye ne-nab-paclitaxel, isigulana sanikwa idosi ye-CT041 engama-250 × 10.⁶iiseli ngoJulayi 2021. Isigulana safumana i-CRS yebanga lesi-2, eyalawulwa ngakumbi nge-tocilizumab. I-PR yafikelelwa ukususela kuvavanyo lokuqala kwiiveki ezi-4 emva kokufakwa. Izilonda ezijoliswe ekugugulekeni kwemiphunga emva koko zanyamalala zaza zafumana impendulo epheleleyo. Ithumba lalisalawulwa kakuhle de kwaba kulandelelwano lokugqibela ngoJulayi 2023. Inombolo yekopi yegazi elingaphandle kwe-CLDN18.2 CAR kuzo zombini izigulana ibonise ukwanda okukhawulezileyo emva kokufakwa, yafikelela kwinqanaba eliphezulu kwiiveki ezi-2. Kwangaxeshanye, iziphumo zokuhlelwa kweeseli ezisebenza nge-fluorescence zibonise ukwanda kweeseli ze-CD8 T zegazi elingaphandle kunye neeseli zeTreg, kunye nokwehla kweeseli ze-CD4 T kunye neeseli ze-B. Olu tshintsho kwiindlela ze-immune cell phenotypes lubonise ukuzingisa okukhulu xa kuthelekiswa notshintsho kumanqanaba e-cytokine.

Okwangoku, kukho ezinye iimvavanyo ezininzi zeklinikhi ze-CAR-T eTshayina, kwaye zikhangela izigulane. Ukuze ufumane iingcebiso ngamayeza amatsha kunye netekhnoloji, ungaqhagamshelana neSebe leMicimbi yeZibhedlele ze-Oncology zaseBeijing South Region.

Inombolo yefowuni: 4008803716

I-imeyile：myimmnet@163.com

Iireferensi

1.https://www.carsgen.com/en/news/carsgen-presents-updated-results-on-satri-cel-in-nature-medicine-and-at-2024-asco/

2.https://www.nature.com/articles/s41591-024-03037-z

3.https://www.carsgen.com/media/fooloi3a/ct041-cg4006-asco-2024_v3-0_20240603.pdf

4. https://jhoonline.biomedcentral.com/articles/10.1186/s13045-023-01491-9