Faomhadh agus infhaighteacht teiripe CAR T-Cell

iúil 2021:  In June 2014, KITE Biotechnology Company, with only 19 employees, was listed on NASDAQ in the United States, and it took 130 million US dollars in one day! Just two months later, Juno Biotechnology had less than 20 employees The company announced that it has successfully raised 130 million US dollars in one lump sum, so Juno has raised more than 300 million in one year! These two small companies have no income and no listed drugs, so why are they so popular with investors and have money sent to them ? Because they have mastered a technology called CAR-T cell therapy, a technology that may cure cancer! Nowadays, the famous CAR-T is mentioned, almost everyone knows this, Immunotherapy has officially entered clinical applications.

Tá dhá theiripe CAR-T ceadaithe ag FDA

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

Taispeánadh go spreagann na cóireálacha seo freagraí suntasacha - is féidir fiú othair ard-ailse nach maireann ach cúpla mí a dhíothú go hiomlán, agus i gcásanna áirithe freagairt go láidir ar feadh míonna nó blianta fiú.

Mar shampla, tá teiripe cille CAR-T leigheasta go rathúil ag Emily, cailín leoicéime, ar feadh 7 mbliana. Tá sí ina hurlabhraí ar an teiripe eipiciúil seo freisin agus tá sí taifeadta sa stair.

Míorúilt na teiripe CAR T-Cell

EMILY - LEUKEMIA GIRL 2019

Dr. CARL JUNE – DEVELOPER OF CAR T-CELL THERAPY

Cad é teiripe CAR T Cell?

Déanann an teiripe seo cealla T imdhíonachta a leithlisiú ó othair, agus déanann siad na cealla seo a innealtóireacht go géiniteach in vitro, agus iad á luchtú le “gabhdóirí antaiginí simléir” (CARanna) a aithníonn antaiginí dromchla cille ailse. Ina dhiaidh sin, déantar leathnú fairsing ar na cealla modhnaithe seo sa tsaotharlann sula ndéantar iad a ionghabháil ar ais san othar. Ann sin, bhí siad cosúil le arm dea-oilte a raibh na hairm is déanaí acu chun ionsaí gan staonadh a sheoladh ar chealla ailse.

Bottleneck na teicneolaíochta CAR-T i siadaí soladacha

However, the reason why it is effective in hematoma is because the meall 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 il-mhóilíní (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.

Dá bhrí sin, ní raibh cealla CAR-T éifeachtach go cliniciúil maidir le tumaí soladacha a chóireáil. Bhí súil ag an bpobal míochaine i gcónaí gur féidir le cealla CAR T spriocanna sonracha nua a fhorbairt le haghaidh siadaí níos daingne.

Briseadh síos i dteiripe CAR-T i gcoinne siadaí soladacha

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!

I measc na ngnáthspriocanna antaigin tá:

Mesothelin, used to treat 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 ailse próstatach, srl.;

Claudin 18.2, used for gastric cancer, ailse pancreatic, Etc.

01 Mesothelin CAR-T

Mesothelin is a cell surface glycoprotein that is highly expressed in various tumors, such as malignant pleural mesothelioma, pancreatic cancer, ailse ovarian 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 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.

Dá bhrí sin, tá an teiripe núíosach seo gníomhach go bitheolaíoch in othair a bhfuil ailse pancreatach orthu, agus tá an staidéar seo fós i dtrialacha cliniciúla (NCT03323944).

02 - B7-H3 “Pan-ailse” CAR-T

Tá glúin nua de theiripe CAR-T le haghaidh siadaí soladacha forbartha ag foireann an Ollaimh Majzner ó Choláiste Leighis Stanford. Seo speisialta Teiripe CAR T-Cell glactar leis mar cheann de na teiripí is geallta toisc go ndíríonn sé ar B7-H3, leibhéal ard antaigin atá i láthair i go leor siadaí soladacha, lena n-áirítear roinnt ailsí óige.

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 medulloblastoma, as well as brain stem tumors (DIPG) that are particularly difficult to treat.

Ina dhiaidh sin, bhunaigh an tOllamh Majzner agus a fhoireann glúin nua de chealla CAR-T-B7-H3 CAR-T trí theicneolaíocht eagarthóireachta géine.

Díreach ina dhiaidh sin, ní fhéadfadh na taighdeoirí fanacht chun an turgnamh ar lucha a thosú. Rinne siad cealla meall daonna a thrasphlandú i lucha chun samhlacha luch iolracha d’ailse na hóige a fhoirmiú. Tugadh B7-H3 do na samhlacha luiche seo Teiripe CAR T-Cell agus grúpa rialaithe CD-19 CAR-T, faoi seach.

Bhí iontas ar gach duine! Dúirt an tOllamh Majzner: "Tá an meall díreach imithe."

03, claudin18.2 CAR-T

Le dhá bhliain anuas, tá éachtaí a bhfuil cáil dhomhanda bainte amach acu, agus an chéad meall soladach ar domhan, ag tumaí soladacha inár dtír Teiripe CAR-T Forbraíodh díriú ar Claudin 18.2.

Is próitéin membrane gastrach-sonrach é Claudin18.2 (CLDN18.2) agus meastar gur sprioc theiripeach fhéideartha é d’ailse gastrach agus do chineálacha ailse eile. Bunaithe ar seo, d’fhorbair taighdeoirí na Síne na chéad chealla CAR-T ar domhan i gcoinne Claudin 18.2.

Ag Comhdháil Bhliantúil ASCO 2019, léirigh nuashonruithe sonraí cliniciúla ar chealla CAR-Claudin 18.2 T d’ailse gastrach / pancreatach gur úsáideadh cealla spriocdhírithe claudin 18.2 CAR T chun 12 chás de adenocarcinoma méadastatach a chóireáil (7 gcás d’ailse gastrach agus 5 chás d’arm pancreatic ailse). Tharla teagmhas díobhálach tromchúiseach, bás a bhain le cóireáil, nó néarthocsaineacht thromchúiseach.

I measc 11 réad meastóireachta:

1 case (gastric adenocarcinoma) completely relieved;

3 chás (adenocarcinoma gastrach

2 chás adenocarcinoma pancreatach, 1 chás) loghadh páirteach;

Bhí 5 chás seasmhach;

Cuireadh 2 chás chun cinn;

Ba é an ráta freagartha oibiachtúil foriomlán ná 33.3%.

Thairis sin, léirigh cealla CAR-Claudin 18.2 T le haghaidh taighde réamhchliniciúil ar ailse gastrach gur féidir le cealla CAR-T atá dírithe ar Claudin 18.2 tumaí gastracha i múnlaí luch a dhíchur go hiomlán gan tocsaineacht lasmuigh den sprioc.

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 siadaí gastrointestinal 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. Aois 18 go 75 bliana, fireann nó baineann;

2. Ábhair a bhfuil siadaí soladacha dearbhaithe go paiteolaíoch acu (ie ailse gastrach chun cinn, ailse acomhal esófagastrach, agus ailse pancreatach) ar theip orthu cóireáil chaighdeánach;

3.Claudin 18.2 staining dearfach IHC;

Saol measta> 4 sheachtain;

Teiripí CAR T-Cell ar earcaíocht chliniciúil

Chomh maith leis an dul chun cinn taighde cliniciúil ceannródaíoch thuasluaite, tá mór-ospidéil intíre i mbun taighde cliniciúil CAR-T ar tumaí éagsúla.

Riachtanais othar: Aois 18-80 bliain d’aois, a bhfuiltear ag súil go mairfidh siad ar feadh 6 mhí ar a laghad (ón athbhreithniú tosaigh ar ábhair go dtí go gcuirtear an chóireáil i gcrích tógann sé 5-6 mhí), i riocht maith go ginearálta, in ann maireachtáil leo féin.

Próiseas iarratais ar earcaíocht CAT T-Cell

1. Preliminary review of materials: pathology report, image examination data within one month, recent liver and kidney function report, recent discharge summary submitted to the CancerFax Medical Department;

2. Comhairliúchán duine le duine: Thug an t-othar féin na hábhair go léir chuig comhairliúchán duine le duine san ospidéal earcaíochta trialach cliniciúla (tuarascáil ar chás, achoimre scaoilte, scannán tuarascála íomháithe);

3. Immuno histochemical detection: detecting tumor cell surface antigens EGFR, MUC1 and mesothelin, one of which is strongly positive (high expression) can apply for CAR T-Cell therapy.

Before the advent of cell therapy, solid tumors, including advanced gastric adenocarcinoma and pancreatic cancer, were usually treated with surgery and radiotherapy and chemotherapy. The incidence of gastric adenocarcinoma accounted for 95% of gastric malignancies, and pancreatic cancer was a common malignant tumor. The tumor with the highest degree, the median survival time and the 5-year survival rate are far lower than other tumors, known as “the king of cancer”.

Mar sin féin, tá atarlú áitiúil nó metastasis ag formhór na n-othar tar éis na hoibríochta. Ina theannta sin, níl an cineál meall urchóideach seo íogair do radaiteiripe agus do cheimiteiripe. Dá bhrí sin, bunaithe ar an teiripe caighdeánach reatha, níl an éifeacht cóireála oiriúnach, agus tá an prognóis thar a bheith bocht. Tabharfaidh teacht an imdhíteiripe níos mó dóchais agus míorúiltí do mharthanas fadtéarmach d’othair níos airde.

Creidimid go láidir, tar éis córas rialála imdhíonachta ceallacha foirfe a thabhairt isteach, go n-osclóidh an tír an doras d’imdhíoniteiripe cheallacha chun leasa níos mó othar ailse, agus beidh imdhíteiripe ceallacha ár dtíre ar an stáitse idirnáisiúnta freisin.

B’fhéidir gur mhaith leat léamh: Teiripe CAR T-Cell sa tSín

Ceisteanna Coitianta maidir le teiripe CAR T-Cell

An bhfuil teiripe cille Car-T ar fáil? Cén ailse a chóireáiltear go príomha

A CAR-T cell immunotherapy has been ceadaithe by the US FDA for the treatment of leukemia and lymphoma. Mar sin féin, níl cóireáil tumaí soladacha ceadaithe fós agus tá sé i dtrialacha cliniciúla faoi láthair

An féidir le cealla Car-T ailse gastric a chóireáil?

Freagair Tá CAR-T d’ailse gastrach ag dul faoi thrialacha cliniciúla faoi láthair in Ailse Beijing. Éilítear ar othair rannáin fíocháin a úsáid laistigh de bhliain leis an ngrúpa turgnamhach chun spriocanna a bhrath go sonrach. Má tá toradh na tástála dearfach, ansin

An bhfuil triail chliniciúil ann maidir le cealla Car-T d’ailse gastrach?

A Déantar trialacha cliniciúla baile de CAR-T d’ailse gastrach, a dhéantar in Ospidéal Ailse Ollscoil Peking. Éilítear ar othair rannáin fíocháin phaiteolaíocha a bheith acu laistigh de bhliain chun spriocanna sonracha a scagadh. Othair atá cláraithe faoi láthair

An féidir le hothair ailse ae páirt a ghlacadh i dtrialacha cliniciúla CAR-T?

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

Déan iarratas ar theiripe CAR T-Cell

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