Ukugunyazwa nokwelashwa kwe-CAR T-Cell

July 2021: NgoJuni 2014, Inkampani ye-KITE Biotechnology, enabasebenzi abangu-19 kuphela, yafakwa ohlwini lwe-NASDAQ e-United States, futhi yathatha izigidi ezingu-130 zamadola aseMelika ngosuku olulodwa! Ezinyangeni ezimbili nje kamuva, i-Juno Biotechnology yayinabasebenzi abangaphansi kuka-20 Le nkampani yamemezela ukuthi ikhulise ngempumelelo amaRandi ayizigidi ezingu-130 ngesamba esisodwa sesamba, ngakho uJuno ukhulise ngaphezu kwezigidi ezingu-300 ngonyaka owodwa! Lezi zinkampani ezimbili ezincane azinayo imali engenayo futhi azinazo izidakamizwa ezisohlwini, pho kungani zithandwa kangaka ngabatshalizimali futhi zithunyelelwa imali? Ngoba sebechwepheshile ubuchwepheshe obubizwa ngokuthi i-CAR-T cell therapy, ubuchwepheshe obungase belaphe umdlavuza! Namuhla, kukhulunywa nge-CAR-T edumile, cishe wonke umuntu uyazi lokhu, i-Immunotherapy ingene ngokusemthethweni izicelo zomtholampilo.

I-FDA ivume ukwelashwa okubili kwe-CAR-T

Currently, two CAR T-cell therapies approved by the FDA, Yescarta and Kymriah, are used to treat leukemia and i-lymphomaNgokulandelana.

Lezi zindlela zokwelashwa zikhonjisiwe ukuthi zenze izimpendulo ezibalulekile-ngisho neziguli ezinomdlavuza eziphambili ezisinda ezinyangeni ezimbalwa zingaqedwa ngokuphelele, futhi kwezinye izimo ziphendula ngokuqinile izinyanga noma ngisho neminyaka.

Isibonelo, u-Emily, intombazane enomdlavuza, welashwe ngempumelelo ukwelashwa kwamaseli we-CAR-T iminyaka engu-7. Ubuye waba ngumkhulumeli walolu hlobo olumangalisayo futhi uqoshwe emlandweni.

Isimangaliso sokwelashwa kwe-CAR T-Cell

EMILY - LEUKEMIA GIRL 2019

UDkt. CARL JUNE – UMthuthukisi WE-CAR T-CELL THERAPY

Kuyini ukwelashwa kwe-CAR T Cell?

Lokhu kwelashwa kuhlukanisa amaseli we-immune T ezigulini, futhi afake lawa maseli ku-vitro, awalayishe ngama- “chimeric antigen receptors” (ama-CAR) abona ama-antigens womdlavuza weseli lomdlavuza. Ngemuva kwalokho, lawa maseli aguquliwe anwetshwa kakhulu elabhoratri ngaphambi kokuba abuyiselwe esigulini. Lapho, babefana nebutho eliqeqeshwe kahle elihlome ngezikhali zakamuva ukuze lihlasele lingapheli amaseli omdlavuza.

I-Bottleneck yobuchwepheshe be-CAR-T kwizicubu eziqinile

However, the reason why it is effective in hematoma is because the isisu cells of hematoma have an ancestral target-CD19 (only stored in tumor cells but not in normal cells), we can easily rely on this target Lead CAR-T cells to find cancer cells and eliminate cancer. A third CAR T-cell therapy targeting an antigen called BCMA is expected to be approved for i-myeloma eminingi (Bluebird) later this year. But there are not so obvious targets in solid tumors that exist only in cancer cells and not in normal cells.

Ngakho-ke, amaseli e-CAR-T awasebenzanga kahle ekwelapheni izicubu eziqinile. Umphakathi wezokwelapha uhlale unethemba lokuthi amangqamuzana e-CAR T angathuthukisa imigomo emisha ethile yezicubu eziqinile.

Ukuphumelela ekwelashweni kwe-CAR-T ngokumelene nezicubu eziqinile

At present, with the change of CAR-T algebra, CAR-T has obvious improvements in proliferation and cytokine release. This technology has finally broken the ice, and more and more clinical trials have begun to try to use CAR-T for solid tumors. Treatment, patients with advanced solid tumors ushered in a warm spring!

Izinhloso ezijwayelekile ze-antigen zifaka:

Mesothelin, used to treat i-mesothelioma, pancreatic cancer, ovarian cancer, lung cancer; CEA, used to treat lung cancer, colon cancer, stomach cancer, breast cancer and pancreatic cancer; MUC-1, used to treat liver cancer, lung cancer , Pancreatic cancer, colon cancer, gastric cancer; GPC3, for the treatment of liver cancer; EGFRvII, for the treatment of gliomas, head and neck tumors; B7-H3, for the treatment of Ewing’s sarcoma, rhabdomyosarcoma, nephroblastoma, nerves Blastoma and medulloblastoma and brain stem tumors (DIPG), which are particularly difficult to treat;

PSMA, used for umdlavuza wendlala, njll.;

Claudin 18.2, used for gastric cancer, umdlavuza pancreatic, Njll

01 IMesothelin CAR-T

Mesothelin is a cell surface glycoprotein that is highly expressed in various tumors, such as malignant pleural mesothelioma, pancreatic cancer, umdlavuza wesibeletho and some lung cancers, and is lowly expressed on the surface of normal pleura, peritoneum and pericardium. CAR-T cells against mesothelin have potential antitumor effects.

The latest results of mesothelin CAR-T therapy published by the University of Pennsylvania at the American Society of Clinical Oncology in 2019 show that a total of 6 patients with refractory metastatic pancreatic duct i-adenocarcinoma were successfully enrolled, and all patients have received 2 or more Multiple treatments. These patients were infused with mesothelin CAR T cells 3 times a week for a total of 9 doses. The results showed that there were 2 patients with stable disease, and their progression-free survival time was 3.8 months and 5.4 months.

Ngakho-ke, le ndlela yokwelapha yenoveli iyasebenza ngokwemvelo ezigulini ezinomdlavuza we-pancreatic, futhi lolu cwaningo lusesezivivinyweni zokwelashwa (i-NCT03323944).

02 - B7-H3 "Pan cancer" CAR-T

Ithimba likaSolwazi Majzner waseStanford Medical College lenze isizukulwane esisha se-CAR-T yokwelapha izimila eziqinile. Lokhu okukhethekile Ukwelashwa kwe-CAR T-Cell idunyiswa njengenye yezindlela zokwelapha ezithembisa kakhulu ngoba ihlose i-B7-H3, izinga eliphakeme le-antigen elikhona kwizicubu eziningi eziqinile, kufaka phakathi eminye umdlavuza wobuntwana.

They screened 388 children’s tumors for testing. The results showed that B7-H3 was present in 84% of the samples (tumor cells). B7-H3 content was very high in 70% of the samples. These include Ewing’s sarcoma, rhabdomyosarcoma, nephroblastoma, neuroblastoma and i-medulloblastoma, as well as brain stem tumors (DIPG) that are particularly difficult to treat.

Ngemuva kwalokho, uSolwazi Majzner nethimba lakhe bakha isizukulwane esisha samaseli e-CAR-T-B7-H3 CAR-T ngobuchwepheshe bokuhlela izakhi zofuzo.

Ngokushesha ngemuva kwalokho, abacwaningi abakwazanga ukulinda ukuqala ukuhlolwa kwamagundane. Bafaka amangqamuzana omuntu wesimila kumagundane ukuze bakhe izinhlobo eziningi zamagundane zomdlavuza wezingane. Lezi zinhlobo zamagundane zinikezwe i-B7-H3 Ukwelashwa kwe-CAR T-Cell neqembu lokulawula le-CD-19 CAR-T, ngokulandelana.

Wonke umuntu wamangala! USolwazi Majzner uthe: “Isigaxa sesivele sanyamalala.”

03, claudin18.2 IMOTO-T

Eminyakeni emibili edlule, izicubu eziqinile ezweni lethu zenze impumelelo edume umhlaba wonke, kanye nesimila sokuqala esiqinile emhlabeni I-CAR-T yokwelapha okubhekiswe kuClaudin 18.2 kwenziwe.

I-Claudin18.2 (CLDN18.2) iyiprotheni ekhethekile yesikhumba futhi ithathwa njengelashwa elingaba nomdlavuza wesisu kanye nezinye izinhlobo zomdlavuza. Ngokuya ngalokhu, abacwaningi baseChina benze amangqamuzana okuqala e-CAR-T emhlabeni ngokulwa noClaudin 18.2.

Engqungqutheleni Yonyaka ka-2019 ASCO, ukuvuselelwa kwedatha yomtholampilo yamaseli e-CAR-Claudin 18.2 T omdlavuza wesisu / we-pancreatic kukhombisile ukuthi amaseli we-claudin abhekiswe ku-18.2 CAR T asetshenziselwe ukwelapha amacala ayi-12 e-metastatic adenocarcinoma (amacala ayi-7 womdlavuza wesisu kanye namacala ama-5 epancreatic umdlavuza). Umcimbi omubi kakhulu, ukufa okuhlobene nokwelashwa, noma i-neurotoxicity ebucayi yenzekile.

Phakathi kwezinto eziyi-11 zokuhlola:

Icala elingu-1 (i-adenocarcinoma yesisu) likhululeke ngokuphelele;

Amacala ama-3 (i-adenocarcinoma esiswini

Amacala ama-2 we-pancreatic adenocarcinoma, icala elilodwa) ukuthethelelwa okuyingxenye;

Amacala ama-5 ayeqinile;

2 amacala aqhubekile;

Izinga lokuphendula lenhloso lilonke belingu-33.3%.

Ngaphezu kwalokho, amaseli e-CAR-Claudin 18.2 T ocwaningo lwangaphambi komdlavuza wesisu akhombisile ukuthi amaseli e-CAR-T abhekiswe kuClaudin 18.2 angaqeda ngokuphelele izicubu zesisu kumamodeli wegundane ngaphandle kobuhlungu obudaluliwe.

The good news is that this trial has been pioneered by the Department of Gastroenterology and Oncology at Peking University Cancer Hospital, which is famous for izimila emathunjini in China, to evaluate autologous humanized anti-claudin 18.2 chimeric antigen receptor T cells in advanced solid tumors. Safety and efficacy. Entry criteria (partial)

1. Uneminyaka eyi-18 kuya kwengama-75, owesilisa noma owesifazane;

2. Izihloko ezinezicubu eziqinile eziqinisekisiwe ukuthi zinezifo (okusho ukuthi umdlavuza othuthukile wesisu, umdlavuza we-esophagogastric junction, nomdlavuza we-pancreatic) abehlulekile ukwelashwa okujwayelekile;

3.Claudin 18.2 IHC ibala okuhle;

Ukuphila okulindelekile> amasonto ayi-4;

Ukwelashwa kwe-CAR T-Cell ekuqashweni kwemitholampilo

Ngaphezu kwenqubekela phambili yocwaningo lomtholampilo oshiwo ngenhla, izibhedlela ezinkulu zasekhaya njengamanje ziqhuba ngenkuthalo ucwaningo lomtholampilo lwe-CAR-T ngezicubu ezahlukahlukene.

Izidingo zesineke: Ubudala beminyaka eyi-18-80 ubudala, okulindeleke ukuthi buphile okungenani izinyanga eziyi-6 (kusukela ekubuyekezweni kokuqala kwezinto kuze kuphele ukwelashwa kuthatha izinyanga ezi-5-6), ngokuvamile zisesimweni esihle, zikwazi ukuzihlalela zodwa.

Inqubo yokufaka isicelo sokuqashwa kwe-CAT T-Cell

1. Ukubuyekezwa kokuqala kwezinto: umbiko we-pathology, idatha yokuhlolwa kwesithombe phakathi nenyanga eyodwa, umbiko wakamuva wokusebenza kwesibindi nezinso, isifinyezo sakamuva sokukhishwa esithunyelwe eMnyangweni Wezokwelapha weCancerFax;

2. Ukubonisana ubuso nobuso: Isiguli uqobo silethe zonke izinto zecala eklinikhi yokuqashwa kwecala lokubonisana ubuso nobuso (umbiko wecala, isifinyezo sokukhishwa, ifilimu yombiko wezithombe);

3. Ukutholwa kwe-Immuno histochemical: ukuthola ama-antigens angaphezulu kweseli yesimila i-EGFR, i-MUC1 ne-mesothelin, enye yawo ehle kakhulu (inkulumo ephezulu) ingafaka isicelo sokwelashwa kwe-CAR T-Cell.

Ngaphambi kokufika kokwelashwa kwamangqamuzana, izimila eziqinile, okuhlanganisa i-adenocarcinoma ethuthukisiwe yesisu kanye nomdlavuza we-pancreatic, ngokuvamile zazilashwa ngokuhlinzwa kanye ne-radiotherapy kanye ne-chemotherapy. Isigameko se-gastric adenocarcinoma sabalelwa ku-95% wezinkinga zesisu, kanti umdlavuza we-pancreatic wawuyisimila esiyingozi esivamile. Isimila esinezinga eliphezulu kakhulu, isikhathi esimaphakathi sokusinda kanye nezinga lokusinda leminyaka emi-5 liphansi kakhulu kunezinye izimila, ezaziwa ngokuthi “inkosi yomdlavuza”.

Kodwa-ke, iziguli eziningi zinokuphindeka kwendawo noma imastastasis ngemuva kokuhlinzwa. Ngaphezu kwalokho, lolu hlobo lwesimila esibulalayo aluzweli kwi-radiotherapy kanye ne-chemotherapy. Ngakho-ke, ngokususelwa ekwelashweni okujwayelekile okujwayelekile, umphumela wokwelashwa awulungile, futhi isibikezelo sibi kakhulu. Ukufika kwe-immunotherapy kuzoletha ithemba eliningi kanye nezimangaliso zokusinda isikhathi eside ezigulini ezithuthuke kakhulu.

Sikholwa ngokuqinile ukuthi ngemuva kokwethulwa kohlelo oluphelele lokulawulwa kwamasosha omzimba, izwe lizovula umnyango we-immunotherapy yamaselula ukuze kuhlomule iziguli ezinomdlavuza eziningi, futhi ne-immunotherapy yeselula yezwe lethu nayo izobe isesigabeni samazwe omhlaba.

Ungahle uthande ukufunda: Ukwelashwa kwe-CAR T-Cell eChina

Ama-FAQ ekwelashweni kwe-CAR T-Cell

Ngabe ukwelashwa ngamaseli eCar-T kuyatholakala? Imuphi umdlavuza welashwa kakhulu

A CAR-T cell immunotherapy has been kuvunyelwe by the US FDA for the treatment of leukemia and lymphoma. Kodwa-ke, ukwelashwa kwezicubu eziqinile akukakamukelwa futhi njengamanje kusezivivinyweni zokwelashwa

Ngabe amaseli e-Car-T angalapha umdlavuza wesisu?

Impendulo I-CAR-T yomdlavuza wesisu njengamanje ibhekene nokuhlolwa komtholampilo eBeijing Cancer. Iziguli kudingeka ukuthi zisebenzise izingxenye zezicubu kungakapheli unyaka owodwa eqenjini lokuhlola ukuthola ukutholwa okuthile. Uma umphumela wokuhlolwa ulungile, khona-ke

Ingabe kukhona ukuhlolwa komtholampilo kwamaseli e-Car-T ngomdlavuza wesisu?

A Kunezivivinyo zokwelashwa zasekhaya ze-CAR-T ngomdlavuza wesisu, owenziwa ePeking University Cancer Hospital. Iziguli kudingeka ukuthi zibe nezingxenye zezicubu zomzimba kungakapheli unyaka owodwa ukuze kuhlolwe izinhloso ezithile. Iziguli ezibhalisiwe njengamanje

Ngabe iziguli ezinomdlavuza wesibindi zingabamba iqhaza ezivivinyweni zokwelashwa ze-CAR-T?

Impendulo According to your main complaint; the clinical application of CAR-T immunotherapy for solid tumors of umdlavuza wesibindi is not approved. The principle of CAR-T is to extract immune cells, and then use in vitro culture

Faka isicelo sokwelashwa kwe-CAR T-Cell

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