satricabtagene autoleucel (Satri-cel,CT041)

I-satricabtagene autoleucel (Satri-cel, CT041) iwumkhiqizo we-CAR T-cell owukhethekayo ngokumelene nephrotheni i-Claudin18.2 enamandla okuba phambili emhlabeni jikelele. I-Satri-cel ihlasela amathumba aqinile e-Claudin18.2 ngokugxila kakhulu kumdlavuza wesisu/umdlavuza we-gastroesophageal junction (GC/GEJ) kanye nomdlavuza we-pancreatic (PC).

Imiphumela yokugcina yokulandelela yesilingo esiqalwe ngumphenyi i-CT041-CG4006 (NCT03874897) se-satricabtagene autoleucel ishicilelwe kuyi-Nature Medicine ngomhlaka-3 Juni 2024.

Iziguli ezingu-98 zihlanganyele kulolu cwaningo, futhi imiphumela ibonise ukuthi izinga lokulawula isifo (i-DCR) laliphezulu lifinyelela ku-91.8%, iziguli ezingu-38 zithole ukuxolelwa, izinga lokuxolelwa lilonke lalingu-38.8%, i-median progression free survival (PFS) yayiyizinyanga ezingu-4.4, i-median overal survival (OS) yayiyizinyanga ezingu-8.8, kanti i-median overal survival (mDOR) yayiyizinyanga ezingu-6.4. Phakathi kweziguli ezingu-90 ezinezilonda eziqondiwe, iziguli ezingu-70 zithole amazinga ahlukahlukene okuncipha kwesimila.

Phakathi kweziguli ezingu-51 ezinomdlavuza wesisu ezelashwe nge-monotherapy nge-Satri-cel, izinga lokulawula lesi sifo laliphezulu lifinyelela ku-96.1% (49), kanti izinga lokuphendula lilonke lalingu-54.9% (28). Phakathi kwazo, iziguli ezingu-27 zithole impendulo engaphelele (PR), isiguli esisodwa sathola impendulo ephelele (CR), kanti ubude besikhathi esimaphakathi (mDOR) babuyizinyanga ezingu-6.4.

Isiphetho

I-Satri-cel ikhombisa amandla okwelapha ngephrofayili yokuphepha elawulekayo ezigulini ezinomdlavuza wesisu othuthukisiwe one-CLDN18.2.

Ngomhlaka-9 Septhemba 2023, amacala amabili okwelashwa komdlavuza we-pancreatic osabalele nge-CARsgen's CT041, i-Claudin (CLDN) 18.2 CAR T-cell Therapy entsha, anyatheliswa kuyi-Journal of Hematology & Oncology enesihloko esithi “CT041 CAR T cell therapy for Claudin18.2 positive metastatic pancreatic cancer”.

Esimweni sokuqala, owesifazane oneminyaka engu-58 ubudala watholakala enomdlavuza we-pancreatic one-metastasis yamaphaphu nama-lymph nodes. I-nab-paclitaxel yomugqa wokuqala kanye ne-gemcitabine kanye ne-irinotecan-liposome yomugqa wesibili kanye ne-5-flurouracil yehlulekile ngaphambi kokuba abhaliswe esivivinyweni sezokwelapha se-CT041, ngemuva kokuqinisekisa ukubonakaliswa kwe-CLDN18.2 njengo-2+/70%. Ngemva kokuncipha kwe-lymphodepletion equkethe i-fludarabine, i-cyclophosphamide, kanye ne-nab-paclitaxel, umthamo we-CT041 ongu-250 × 10⁶Amaseli anikezwa isiguli ngoSepthemba 2021. I-Grade 2 cytokine release syndrome (CRS) yavela, kamuva eyalawulwa yi-tocilizumab. Impendulo engaphelele (PR) yafinyelelwa ngokusho kwe-RECIST v1.1, kanye nokuncipha okukhulu kokusabalala kwamaphaphu.

Esimweni sesi-2, owesifazane oneminyaka engu-75 ubudala watholakala enomdlavuza we-pancreas we-pT2N0 ngemuva kokuhlinzwa ngoMeyi 2019. Ukwanda kwe-lung metastasis kwatholakala ngemuva kwezinyanga ezi-5 ngesikhathi sokulandelela okuvamile ngemva kokuhlinzwa. I-S-1 monotherapy yanikezwa njenge-chemotherapy yokuqala kusukela ngoDisemba 2019. Ngesikhathi sokwelashwa ngemisebe yokwelapha endaweni yokuhlinzwa, ukuqhubeka kwe-tumor kwabonakala emaphashini. Njengoba ukubonakaliswa kwe-CLDN18.2 kwatholakala njengo-3+/60%, isiguli sabhaliswa esivivinyweni sezokwelapha se-CT041. Ngemva kokuthola i-lymphodepletion equkethe i-fludarabine, i-cyclophosphamide kanye ne-nab-paclitaxel, isiguli sanikwa umthamo we-CT041 ongu-250 × 10.⁶amaseli ngoJulayi 2021. Isiguli sathola i-CRS yebanga lesi-2, eyalawulwa kakhulu nge-tocilizumab. I-PR yafinyelelwa kusukela ekuhlolweni kokuqala emavikini ama-4 ngemuva kokufakwa. Izilonda eziqondiwe zokusabalala kwamaphaphu zanyamalala kamuva futhi zathola impendulo ephelele. Isimila sasisalawulwa kahle kwaze kwaba yilapho kulandelwa okokugcina ngoJulayi 2023. Inombolo yekhophi yegazi elingaphandle kwe-CLDN18.2 CAR kuzo zombili iziguli ibonise ukwanda okusheshayo ngemva kokufakwa, kwafinyelela phezulu emavikini ama-2. Ngesikhathi esifanayo, imiphumela yokuhlunga amaseli enziwe nge-fluorescence ibonise ukwanda kwamaseli egazi angaphandle kwe-CD8 T namaseli e-Treg, kanye nokwehla kwamaseli e-CD4 T namaseli e-B. Lokhu kushintsha kwe-phenotypes yamaseli omzimba kubonise ukuphikelela okukhulu uma kuqhathaniswa nokushintsha kwamazinga e-cytokine.

Njengamanje, kunezinye izivivinyo eziningi ze-CAR-T eShayina, futhi zifuna iziguli. Ukuze uthole ukubonisana ngemithi emisha kanye nobuchwepheshe, ungaxhumana noMnyango Wezizwe Ngezizwe Wesibhedlela iBeijing South Region Oncology.

Inombolo yocingo: 4008803716

I-imeyili：myimmnet@163.com

Izinkomba

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