Kliniki yekuyedza kunyorera Bhora CAR T-Cell kurapwa

16th Kurume 2023: Kurapwa kwegomarara kuri kuvandudzwa nemishonga mitsva yeimmunotherapeutic inonangana neiyo microenvironment panzvimbo yebundu. T masero ane chimeric antigen receptors (CAR) ari kuongororwa zvakanyanya nezve cancer immunotherapy. Tisagenlecleucel, rudzi rweCD19-specific CAR-T cell, ichangobva kugamuchira mvumo yekiriniki. Dhizaini dzeCAR dzakanangidzirwa pane zvitsva zvinangwa zvine chekuita nehematological uye yakasimba malignancies zviri kuedzwa mukuenderera mberi. kliniki miedzo. 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.

Kuvandudzwa kwemasero eCAR-T kuri kufambira mberi nekushandiswa kwepasi rose uye T cell receptor-engineered CAR-T masero. Muchidzidzo ichi, takanyoresa miedzo yekiriniki yemasero eCAR-T kuChina, takaongorora zvivakwa zveCAR, uye tikapa muchidimbu mamiriro ekudzidza eCAR-T muChina.

Nzvimbo ye CAR T-Cell kurapa muChina yakakura nokukurumidza zvikuru mumakore mashoma apfuura. Recruitment for CAR T-Cell kurapa kwekiriniki miedzo dziri kuenderera mberi kune dzimwe nzvimbo dzinotungamira gomarara muChina. Dzakanyorwa ndedzimwe dzenzvimbo muChina dziri kuita iyi miedzo yekiriniki:

1. Tianjin Hematology Hospital (Legend Bio)
2. Anhui Provincial Hospital (Masero: Bioheng)
3. Peking University Hospital, Shenzhen (Masero: Bioheng)
4. The 1st Affiliated Hospital yeSoochow University (Unicar-Therapy)
5. The 3rd Xiangya Hospital yeCentral South University (Unicar-Therapy)

Kupindira / Kurapa : CD19-yakanangana Chimeric Antigen Receptor (CAR) T Masero

Rondedzero yakazara:

Kuongororwa kwedosi kwechidzidzo ichi kuchava dhizaini ye3 + 3 ine tarisiro yeDLT rate ye <1/3. Kuongororwa kwedosi kunogona kuregedzerwa kamwe chete kana mamwe mazinga edosi ane inogamuchirwa chengetedzo mbiri uye inogutsa antitumor chiitiko chakasarudzwa kuti chiongororwe. Iyo yakanyanya kushivirira dose (MTD) inogona kusawanikwa pamatanho edosi akafanotemerwa muchidzidzo ichi, sezvakatsanangurwa pazasi.

Munguva yekurapa kwechidzidzo, madosi mana emazinga eJWCAR029 achaongororwa. kunyoreswa kuchatanga padanho redhijitari 1, tevera 3 + 3 dose exploration design protocol, uye pakupedzisira sarudza imwe kana kupfuura dhigirii nhanho ine inogamuchirika chengetedzo chimiro uye yakanaka antitumor basa seyero yakakurudzirwa, mushure meiyo dosi yekuongorora icharegedzwa.

Dose inodzikamisa chepfu (DLT) inozoongororwa mukati memazuva makumi maviri nemasere mushure meJWCAR28 infusion. Yega yega dosi cohort yakarongerwa kunyoresa zvidzidzo zvitatu pakutanga, uye chidzidzo chimwe chevana chiri pasi pemakore gumi ezera chinogona kuongororwa DLT chichanyoreswa padanho rega rega redosi. Muchikamu chekutanga chedosi, zvidzidzo zvitatu zvekutanga zvichaiswa zvishoma nemazuva gumi nemana. Pamwero wega wega wepamusoro wedosi, varwere vatatu vekutanga mukati meiyo dosi cohort vanorapwa angangoita mazuva manomwe vakaparadzana. Kune mazinga edosi anoonekwa akachengeteka, zvingangoita 029 zvidzidzo zvine DLT inoongororwa zvinofanirwa kupedzisa 10-zuva DLT yekuongorora nguva.

Inosanganisira Maitiro:

1. Zera ≤ makore makumi matatu uye uremu ≥30kg.
2. Varwere vane r/r B-ALL, inotsanangurwa sechirwere chemorphological mumwongo (≥5% kuputika) uye chimwe chezvinotevera:
   • ≥2 BM kudzokerazve;
   • Refractory inotsanangurwa sekudzokazve kana kuregererwa kwekutanga <mwedzi ye12 kana kusawana CR mushure me1 cycle ye-standard induction chemotherapy regimen ye relapsed leukemia;-primary chemo-refractory sezvinotsanangurwa nekusawana CR mushure me 1 kutenderera kwekomisheni chemotherapy kana 2 cycles. a standard induction chemotherapy regimen ye relapsed leukemia;
   • Chero chero BM inodzokera shure mushure meHSCT iyo inofanira kuva ≥90 mazuva kubva kuHSCT panguva yekuongororwa, uye inodiwa kuti isunungurwe kubva kuGVHD uye kupera kubva kune chero immunosuppressive therapy ≥1 mwedzi panguva yekuongorora;
   • Varwere vane Ph+ VESE vanokodzera kana vasingashiviriri kana kuti vakundikana mitsetse miviri yeTKI therapy, kana kana TKI therapy ikapikiswa.
   Ongorora: Varwere vane MRD + mushure mekuvharisa kurapwa vanobvumidzwa kurapwa.
3. Karnofsky (zera ≥16 makore) kana Lansky (makore <16 makore) maitiro ekuita> 60.
4. Kushanda kwenhengo yakakwana.
5. Vascular access yakakwana kune leukocyte isolation.
6. Inotarisirwa nguva yekupona > 3 mwedzi.
7. Chero isiri-hematological chepfu nekuda kwekurapwa kwekare, kunze kwealopecia uye peripheral neuropathy, inofanira kudzoserwa ku ≤ giredhi 1.
8. Vanhukadzi vane mikana yekuzvara (vese vanhukadzi vanokwanisa kubata pamuviri) vanofanira kubvuma kushandisa nzira inonyatsoshanda yekudzivirira kubata pamuviri kwegore rimwe zvichitevera kuiswa kweJWCAR1; vanhu vechirume vane vavakaroorana navo vanogona kubereka vana vanofanira kubvuma kushandisa nzira inobudirira yekudzivirira kubata pamuviri kwegore rimwe zvichitevera kuiswa kweJWCAR029.

Kuregererwa Criteria:

1. Vanhu vane leukemia mukati mepakati tsinga system (CNS) vane inoshanda CNS maronda uye akakosha neurodegenerative zviratidzo, kana vanhu vane CNS giredhi iri pakati peCNS-2 neCNS-3 zvinoenderana neNCCN nhungamiro (vanhu vane CNS giredhi CNS-2 nekuda kwe kukuvara kwepuncture kunogona kunyoreswa).
2. Iripo kana yapfuura kiriniki yakakosha CNS maronda akadai sepfari, pfari pfari, kuoma mitezo, aphasia, cerebral edema, sitiroko, kukuvara kwakanyanya kwehuropi, dementia, chirwere cheParkinson, cerebellar chirwere, organic brain syndrome, psychosis, nezvimwe.
3. Varwere vane genetic syndromes kunze kweDown syndrome.
4. Varwere vane Burkitt's lymphoma.
5. Nhoroondo yehuipi kunze kweB-ALL kweinenge 2 makore asati anyoreswa.
6. Musoro uyu aive neHBV, HCV, HIV kana syphilis utachiona panguva yekuongororwa.
7. Nyaya ine yakadzika vein thrombosis (DVT) (cancer thrombosis kana thrombosis) kana pulmonary artery embolism (PE) kana iri paanticoagulation therapy yeDVT kana PE mukati memwedzi mitatu isati yasaina fomu remvumo rine ruzivo.
8. isingadzoreki systemic fungal, bhakitiriya, hutachiona kana humwe hutachiona.
9. Kusanganiswa kweanoshanda autoimmune zvirwere zvinoda immunosuppressive therapy.
10. Chirwere chakanyanya kana chisingaperi chegraft-versus-host.
11. Nhoroondo yeimwe yeinotevera chirwere chemwoyo mukati memwedzi ye6 yapfuura: Kirasi III kana IV kukundikana kwemoyo sezvinotsanangurwa neNew York Heart Association (NYHA), cardiac angioplasty kana stenting, myocardial infarction, angina isina kugadzikana, kana imwe kliniki inokosha yemwoyo chirwere.
12. Vakadzi vane mimba kana vanoyamwisa. Vakadzi vane mikana yekuzvara vana vanofanirwa kuve neserum pregnancy test isina kunaka mukati memaawa makumi mana nemasere vasati vatangwa lymphocyte clearance chemotherapy.
13. Kurapwa kwekare neCAR-T maseru kana mamwe maT masero akagadziridzwa.
14. Kare anti-CD19/anti-CD3 therapy, kana chero imwe anti-CD19 therapy.
15. Mishonga yakakodzera kana marapiro mukati menguva yakatarwa.
16. kuvapo kwezvimwe zvinhu izvo, mumaonero emuongorori, zvingaita kuti zvive zvakaoma kana kuti zvisingabviri kuti munhu aite maererano neprotocol, zvakadai sehutano husingadzoreki, hwepfungwa, hwemhuri, hwemagariro evanhu, kana mamiriro enzvimbo, pamwe nekusada kana kusakwanisa kuita. saka.
17. Zvinozivikanwa zvekusawirirana nehupenyu zvinotyisa, hypersensitivity reaction, kana kusashivirira kuJWCAR029 cell formulation kana zvinoriumba.

Disclaimer

Chidzidzo chakanyorwa pawebhusaiti iyi hazvireve kuti zviremera zvakazviongorora. Kuchengeteka uye kuve nechokwadi kwesainzi kwechidzidzo chakanyorwa pano ibasa remutsigiri wechidzidzo nevaongorori. Ziva njodzi uye zvingangobatsira zvezvidzidzo zvekiriniki, uye taura nemutarisiri wako wehutano usati watora chikamu.

Vatsigiri vezvidzidzo uye vaongorori ndivo vane basa rekuona kuti zvidzidzo izvi zvinoteedzera mitemo nemirau yese uye zvinopa ruzivo pawebhusaiti. Vashandi veNLM havaone chokwadi chesainzi kana kukosha kweruzivo rwakatumirwa kunze kwekungodzokororwa kwemhando yepamusoro yezvikanganiso zviri pachena, zvikanganiso, kana kusawirirana.

Kusarudza kutora rutivi mufundo chisarudzo chinokosha chomunhu oga. Musati mapinda muchidzidzo, kurukurai nezvese zvingasarudzwa nemutarisiri wenyu wehutano nevamwe vanachipangamazano vakavimbika. Kuti uwane rumwe ruzivo nezve kutora chikamu muzvidzidzo zvekiriniki, ona Dzidza Nezve Clinical Zvidzidzo, izvo zvinosanganisira mibvunzo yaungade kubvunza usati wafunga kutora chikamu muchidzidzo.