satricabtagene autoleucel (Satri-cel,CT041)

Satricabtagene autoleucel (Satri-cel, CT041) ndi mankhwala a autologous CAR T-cell omwe amatsutsana ndi puloteni ya Claudin18.2 yomwe ili ndi kuthekera kokhala pamwamba padziko lonse lapansi. Satri-cel imayang'ana kwambiri zotupa zolimba za Claudin18.2 zomwe zimayang'ana kwambiri khansa ya m'mimba/gastroesophageal junction (GC/GEJ) ndi khansa ya kapamba (PC).

Zotsatira zomaliza za kafukufuku woyambitsidwa ndi ofufuza CT041-CG4006 (NCT03874897) wa satricabtagene autoleucel zasindikizidwa mu Nature Medicine pa June 3, 2024.

Odwala onse 98 adatenga nawo gawo mu kafukufukuyu, ndipo zotsatira zake zidawonetsa kuti kuchuluka kwa matenda (DCR) kunali kokwera kufika pa 91.8%, odwala 38 adachira, kuchuluka kwa kuchira konse kunali 38.8%, kupulumuka kwapakati kwaulere (PFS) kunali miyezi 4.4, kupulumuka kwapakati (OS) kunali miyezi 8.8, ndipo nthawi yapakati ya kuchira (mDOR) inali miyezi 6.4. Pakati pa odwala 90 omwe adadwala matendawa, odwala 70 adachira mosiyanasiyana.

Pakati pa odwala 51 omwe adalandira chithandizo cha khansa ya m'mimba ndi Satri-cel, kuchuluka kwa matenda omwe adatenga kunali kokwera kufika pa 96.1% (49), ndipo kuchuluka kwa mayankho onse kunali 54.9% (28). Pakati pawo, odwala 27 adalandira yankho la gawo (PR), wodwala m'modzi adalandira yankho lathunthu (CR), ndipo nthawi yapakati ya yankho (mDOR) inali miyezi 6.4.

Mapeto

Satri-cel ikuwonetsa kuthekera kochiritsira ndi chitetezo chodalirika mwa odwala omwe ali ndi khansa ya m'mimba yotsogola ya CLDN18.2.

Pa Seputembala 9, 2023, milandu iwiri ya chithandizo cha khansa ya kapamba yofalikira ndi CARsgen's CT041, njira yatsopano yochiritsira ya Claudin (CLDN) 18.2 CAR T-cell Therapy, idasindikizidwa mu Journal of Hematology & Oncology yotchedwa “CT041 CAR T cell therapy for Claudin18.2 positive metastatic pancreatic cancer”.

Pa mlandu woyamba, mayi wazaka 58 anapezeka ndi khansa ya kapamba yomwe inali ndi ma cell a m'mapapo ndi ma lymph nodes. Nab-paclitaxel yoyamba pamodzi ndi gemcitabine ndi irinotecan-liposome yachiwiri pamodzi ndi 5-flurouracil zinalephera kulembedwa mu kafukufuku wa CT041, atatsimikizira kuti CLDN18.2 inali 2+/70%. Pambuyo pa lymphodepletion yokhala ndi fludarabine, cyclophosphamide, ndi nab-paclitaxel, mlingo wa CT041 wa 250 × 10.⁶Maselo anaperekedwa kwa wodwalayo mu Seputembala 2021. Matenda a cytokine release syndrome (CRS) a Giredi 2 adachitika, omwe pambuyo pake adawongoleredwa ndi tocilizumab. Kuyankha pang'ono (PR) kudachitika malinga ndi RECIST v1.1, ndi kuchepa kwakukulu kwa kufalikira kwa mapapo.

Pa mlandu wachiwiri, mayi wazaka 75 anapezeka kuti ali ndi khansa ya kapamba ya pT2N0 atachitidwa opaleshoni mu Meyi 2019. Kufalikira kwa mapapo kunapezeka patatha miyezi 5 panthawi yotsatiridwa ndi dokotala pambuyo pa opaleshoni. Chithandizo cha S-1 chinaperekedwa ngati mankhwala oyamba a chemotherapy kuyambira Disembala 2019. Pa nthawi ya opaleshoni, kukula kwa chotupa kunawonedwa m'mapapo. Popeza CLDN18.2 inapezeka kuti ndi 3+/60%, wodwalayo analembetsa mu mayeso azachipatala a CT041. Atalandira lymphodepletion yokhala ndi fludarabine, cyclophosphamide ndi nab-paclitaxel, wodwalayo anapatsidwa mlingo wa CT041 wa 250 × 10.⁶Mu Julayi 2021, wodwalayo adakumana ndi CRS ya giredi 2, yomwe idawongoleredwanso ndi tocilizumab. PR idapezeka kuyambira pomwe adayesedwa koyamba milungu 4 atalandira chithandizo. Zilonda zomwe zidafalikira m'mapapo pambuyo pake zidasowa ndipo zidayamba kuchira kwathunthu. Chotupacho chinali chikuyang'aniridwabe mpaka pomwe adatsatira komaliza mu Julayi 2023. Nambala ya CLDN18.2 CAR m'magazi onse awiri idawonetsa kuwonjezeka mwachangu pambuyo pa chithandizo, zomwe zidafika pachimake mkati mwa milungu iwiri. Nthawi yomweyo, zotsatira za kusanja maselo zomwe zidayambitsidwa ndi fluorescence zidawonetsa kuwonjezeka kwa maselo a CD8 T m'magazi am'mimba ndi maselo a Treg, pamodzi ndi kuchepa kwa maselo a CD4 T ndi maselo a B. Kusintha kumeneku mu mawonekedwe a maselo oteteza thupi kunawonetsa kupirira kwakukulu poyerekeza ndi kusintha kwa kuchuluka kwa cytokine.

Pakadali pano, pali mayeso ena ambiri azachipatala a CAR-T ku China, ndipo akufunafuna odwala. Kuti mumve zambiri za mankhwala ndi ukadaulo watsopano, mutha kulumikizana ndi Dipatimenti Yapadziko Lonse ya Chipatala cha Oncology ku Beijing South Region.

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Zolemba

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