Unyango lwe-CAR-T lomhlaza wesisu

I-Claudin18.2 (CLDN18.2) yi-isoform yeprotheyini edibeneyo ebonakala ngokukodwa kwi-epithelium yesisu kwaye ibonakaliswa kakhulu kumphezulu weeseli zomhlaza wesisu. I-CT041 (ikhowudi yophuhliso i-CG4006) yimveliso ye-CAR-T ejolise kwi-CLDN18.2. Idatha yeSigaba soku-1 ibonisa umsebenzi othembisayo wokulwa nethumba kwizigulana ezinomhlaza wesisu ezinyangwe kakhulu, ezine-CLDN18.2.

Ukwanda koxinzelelo lwe-HER2 kukwabonakala nakwiqela labantu abanesifo somhlaza wesisu. Unyango lwe-CAR-T olujoliswe kwi-HER2 lubonakalise amandla okulwa nomhlaza kwizifundo zangaphambi konyango kunye nezokuqala zonyango. I-TAC01-HER2 ye-Triumvira Immunologics okwangoku ikuvavanyo lwezonyango lweSigaba sesiBini.

• Ukujolisa Okujolise Ngokuthe NgqoNgokuyalela iiseli ze-CAR-T kwi-CLDN18.2 okanye kwi-HER2, iiseli zomhlaza wesisu zinokuchongwa ngokuchanekileyo kwaye zisuswe, nto leyo enciphisa iziphumo ezingaphandle kwethumba.

• Ukoyisa ukuxhathisa unyango olunemiqolo emininzi: Kwizilingo ze-CT041, iqela lomhlaza wesisu lifumene izinga lokuphendula ngendlela echanekileyo (ORR) elingama-57.1%, izinga lokulawula izifo (DCR) elingama-75.0%, kunye nokusinda kweenyanga ezi-6 (OS) okungama-81.2% kwizigulana eziye zasilela kwiindlela ezininzi zonyango zangaphambili.

• Iimpendulo Ezihlala Ixesha ElideUnyango lwe-CLDN18.2-CAR-T luvelise ithuba lokuphendula leenyanga ezi-6 le-44.8%, nto leyo ebonisa ukuba kunokwenzeka ukuba kubekho inzuzo yezonyango yexesha elide.

• Unyango oluKhethekileyoUkusebenzisa ii-T cells zesigulana kunciphisa umngcipheko wokwaliwa kwaye kuphucula ukhuseleko kunye nokusebenza kakuhle.

• Ukuqokelelwa kweeseli ze-T zegazi ezingaphandle
  Iiseli ze-T zahlulwe kwigazi elingaphandle kwesigulana nge-leukapheresis.

• Ubunjineli beMvelo
  Kwilabhoratri ehambelana ne-GMP, ii-T cells ziguqulwa ukuze ziveze i-CAR ejolise kwi-CLDN18.2 okanye kwi-HER2, emva koko zandiswe kwi-ex vivo.

• Ukulungisa i-Lymphodepleting
  Kusetyenziswa indlela yokulungiselela i-cyclophosphamide kunye ne-fludarabine ukuze kuncitshiswe ii-lymphocytes zendalo kwaye kudale indawo efanelekileyo yokwandiswa kweeseli ze-CAR-T.

• Ukufakwa kweeSeli zeCAR-T
  Iiseli ze-CAR-T ezakhiwe ngobunjineli zibuyiselwa kwisigulana ngemithambo yegazi.

• Ukubeka iliso kunye noLawulo
  Emva kokufakwa, izigulane zijongwa ngokusondeleyo ukuba azifumani i-cytokine release syndrome (CRS) kunye ne-neurotoxicity, kwaye zithathe amanyathelo afanelekileyo xa kufuneka.

• Uhlalutyo lweSigaba soku-1 se-CT041 (CLDN18.2-CAR-T)
  Phakathi kwezigulane ezingama-37 ezazinyangwe kakhulu ngaphambi kokuba zifumane unyango, iqela elincinci lomhlaza wesisu lifumene i-ORR engama-57.1%, i-DCR engama-75.0%; ama-94.6% aye afumana i-CRS yeBanga loku-1 ukuya kwelesi-2 kuphela, engenazo i-CRS yeBanga lesi-3 okanye ngaphezulu okanye i-neurotoxicity; ixesha leempendulo zeenyanga ezi-6 yayiyi-44.8%.

• Iziphumo zokugqibela zeSigaba soku-1 zeSatri-cel (ekwajolise kwi-CLDN18.2)
  Kwizigulane ezingama-98 ezine-CLDN18.2-positive gastrointestinal cancer, i-ORR yayiyi-38.8%, i-DCR yayiyi-91.8%; ukusinda okuphakathi okungenankqubela phambili (mPFS) yayiyi-4.4 iinyanga (95% CI 3.7–6.6), ukusinda okuphakathi (mOS) yayiziinyanga eziyi-8.8 (95% CI 7.1–10.2); Ama-96.9% afumene kuphela i-CRS yeBanga loku-1–2, ngaphandle kwe-CRS yeBanga lesi-3+ okanye ukufa okunxulumene noko.

• Idatha yezonyango yasekuqaleni ye-HER2-CAR-T
  Uphononongo lweSigaba soku-1 lokuqala ebantwini lubonise iprofayili yokhuseleko elawulekayo; uvavanyo lokubhalisa lweSigaba sesi-2 luyaqhubeka.

• Iqonga leTekhnoloji eliPhambili
  I-BIOOCUS isebenzisa indawo yokuvelisa iiseli zonyango lwe-GMP yamazwe ngamazwe, iqinisekisa ukuveliswa kweeseli ze-CAR-T okusebenzayo nokungaguquguqukiyo.

• Iqela leeNgcali eziNxulumene neMicimbi eyahlukahlukeneyo
  Iqela lethu liquka iingcali ezinamava kwi-immunology, i-oncology, kunye nonyango lweeseli, ezibonelela ngolawulo olupheleleyo olulungiselelwe wena.

• Amava eKliniki eHlabathi
  Siye sanyanga izigulana ezivela kwihlabathi liphela, siqokelela ulwazi olubanzi malunga nokhuseleko kunye nokusebenza kakuhle kwale nkqubo.

• Inkonzo epheleleyo yokuphela kwesiphelo
  Ukususela kuyilo lweprotocol kunye nokulungelelaniswa konyango lwaphesheya ukuya kulandelelwano lwexesha elide emva kokufakwa kwe-infusion, i-BIOOCUS inikezela ngenkxaso-ndawonye.