CAR oggolaanshaha daaweynta T-Cell iyo helitaanka

July 2021: Bishii Juun 2014, Shirkadda KITE Biotechnology, oo leh 19 shaqaale ah, ayaa lagu qoray NASDAQ ee Maraykanka, waxayna qaadatay 130 milyan oo doolarka Maraykanka ah hal maalin! Laba bilood oo kaliya ka dib, Juno Biotechnology waxay lahayd wax ka yar 20 shaqaale ah Shirkaddu waxay ku dhawaaqday inay si guul leh u ururisay 130 milyan oo doolarka Maraykanka ah hal mar lacag ah, sidaas darteed Juno waxay ururisay in ka badan 300 milyan hal sano! Labadan shirkadood ee yaryar ma haystaan ​​dakhli iyo dawooyin liiska ku jira, markaa maxay caan ugu yihiin maalgashadayaasha oo lacag loogu soo diro? Sababtoo ah waxay ku guulaysteen farsamada loo yaqaan CAR-T cell therapy, tignoolajiyada laga yaabo inay daaweyso kansarka! Maalmahan, CAR-T caanka ah ayaa la sheegay, ku dhawaad ​​qof kastaa wuu ogyahay tan, Immunotherapy waxay si rasmi ah u gashay codsiyada bukaan-socodka.

FDA waxay ansixisay laba daaweyn CAR-T ah

Currently, two CAR T-cell therapies approved by the FDA, Yescarta and Kymriah, are used to treat leukemia and qanjiro, siday u kala horreeyaan.

Daaweyntan waxaa lagu muujiyey inay keenaan jawaabo muhiim ah - xitaa bukaanka kansarka ee horumarsan ee ka badbaada kaliya dhowr bilood ayaa gebi ahaanba la tirtiri karaa, mararka qaarkoodna si adag ayey uga jawaabaan bilo ama xitaa sannado.

Tusaale ahaan, Emily, oo ah gabadh leukaemia ah, waxaa si guul leh u bogsiiyey daaweynta unugga CAR-T muddo 7 sano ah. Waxay sidoo kale noqotay afhayeenka daaweyntan epic waxaana lagu diiwaan geliyay taariikhda.

Mucjisada daaweynta CAR T-Cell

EMILY - LEUKEMIA GIRL 2019

Dr. CARL JUNE - HORUMARKA DAAWAYNTA T-CELL-KA BAabuurka

Waa maxay daaweynta CAR T Cell?

Daaweyntani waxay kala soocaysaa unugyada difaaca T ee bukaanka, iyo hiddo ahaan injineernimada unugyadan ku jira fitamiinada, iyaga oo ku rakibaya "chimeric antigen receptors" (CARs) oo aqoonsada unugyada kansarka dusha sare ee antigens. Ka dib, unugyadan wax laga beddelay waxay ku socdaan ballaarin ballaadhan shaybaarka ka hor inta aan dib loogu soo celin bukaanka. Halkaas, waxay la mid ahaayeen ciidan si wanaagsan loo tababbaray oo lagu qalabeeyay hubkii ugu dambeeyay si ay weerar aan kala joogsi lahayn ugu qaadaan unugyada kansarka.

Bottleneck tiknoolajiyadda CAR-T ee burooyinka adag

However, the reason why it is effective in hematoma is because the buro 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 Meelo badan (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.

Sidaa darteed, unugyada CAR-T ma aysan aheyn kuwo caafimaad ahaan waxtar u leh daaweynta burooyinka adag. Bulshada caafimaadku had iyo jeer waxay rajeyneysaa in unugyada CAR T ay horumarin karaan bartilmaameedyo gaar ah oo cusub oo loogu talagalay burooyinka adag ee adag.

Horumar ku saabsan daaweynta CAR-T ee ka dhanka ah burooyinka adag

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!

Bartilmaameedyada antigen ee caadiga ah waxaa ka mid ah:

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 kansarka qanjirka 'prostateiwm;

Claudin 18.2, used for gastric cancer, kansarka ganaca, IWM

01 Mesothelin CAR-T

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

Sidaa darteed, daaweyntan cusubi waa mid bayooloji ahaan ugu firfircoon bukaanada qaba kansarka ganaca, daraasadani wali waxay ku jirtaa tijaabooyinka bukaan socodka (NCT03323944).

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

Kooxda Professor Majzner oo ka socda Stanford Medical College ayaa soo saaray jiil cusub oo ah daawaynta CAR-T ee burooyinka adag. Kan gaarka ah Daaweynta T-Cell-ka Baabuurka waxaa lagu amaanay inay tahay mid ka mid ah daaweynta ugu rajada badan maxaa yeelay waxay bartilmaameedsaneysaa B7-H3, heer sare oo antigen ah oo ku jira burooyin badan oo adag, oo ay ku jiraan qaar ka mid ah kansarka caruurta.

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.

Intaa ka dib, Professor Majzner iyo kooxdiisu waxay sameeyeen jiil cusub oo unugyada CAR-T-B7-H3 CAR-T iyada oo loo marayo tiknoolajiyada tifaftirka hidda-wadaha.

Isla markiiba ka dib, cilmi baarayaashu way sugi kari waayeen inay ku bilaabaan tijaabada jiirka. Waxay ku beeleen unugyada burooyinka bini'aadamka jiirarka si ay u sameeyaan qaabab badan oo jiir ah oo kansarka carruurnimada ah. Noocyadan jiirka ah waxaa la siiyay B7-H3 Daaweynta T-Cell-ka Baabuurka iyo kooxda xakamaynta CD-19 CAR-T, siday u kala horreeyaan.

Qof walba wuu yaabay! Borofisar Majzner ayaa yiri: "Burooyinka ayaa hadda la waayay."

03, claudin18.2 CAR-T

Labadii sano ee la soo dhaafay, burooyinka adag ee ka jira dalkeenna waxay gaareen guulo adduunka laga wada yaqaan, iyo buro tii ugu horreysay ee adduunka soo marta Daaweynta CAR-T beegsashada Claudin 18.2 ayaa la soo saaray.

Claudin18.2 (CLDN18.2) waa borotiinka xuubka gaarka u ah caloosha waxaana loo tixgeliyaa bartilmaameedka daaweynta kansarka caloosha iyo noocyada kale ee kansarka. Iyadoo taas laga duulayo, cilmi baarayaasha Shiinaha ayaa soo saaray unugyadii ugu horreeyay adduunka ee CAR-T ee ka dhanka ah Claudin 18.2.

Shirka sanadlaha ah ee ASCO 2019, cusbooneysiinta xogta kiliinikada ee unugyada CAR-Claudin 18.2 T ee loogu talagalay kansarka caloosha / qanjirada ayaa muujisay in unugyada bartilmaameedka ah ee loo yaqaan 'claudin 18.2 CAR T cells' loo isticmaalay in lagu daaweeyo 12 xaaladood oo ah metastatic adenocarcinoma (7 kiisaska kansarka caloosha iyo 5 xaaladood oo ganaca ah) kansarka). Dhacdo halis ah oo daran, dhimasho la xiriirta daaweyn, ama neerotoksiko daran ayaa dhacday.

11 ka mid ah walxaha qiimaynta:

1 kiis (adenocarcinoma gastric) oo si buuxda loo nafisiyay;

3 xaaladood (gastric adenocarcinoma

2 xaaladood oo loo yaqaan 'adenocarcinoma' oo loo yaqaan 'pancreatic', 1 kiis) qayb ahaan laga cafiyo;

5 kiis ayaa xasilloonaa;

2 kiis ayaa horumar laga gaadhay;

Heerka jawaabta ujeeddada guud waxay ahayd 33.3%.

Intaa waxaa sii dheer, unugyada CAR-Claudin 18.2 T ee loogu talagalay baaritaanka hore ee kansarka caloosha ayaa muujiyay in unugyada CAR-T ee lagu bartilmaameedsaday Claudin 18.2 ay gebi ahaanba baabi'in karaan burooyinka caloosha ku jira ee moodooyinka jiirka oo aan lahayn sunta ka baxsan bartilmaameedka.

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 burooyinka caloosha iyo mindhicirka 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. Da'da 18 illaa 75 sano, lab ama dhaddig;

2. Mawduucyada cuduro adag lagu xaqiijiyey jir ahaan (sida kansarka caloosha ee horumarsan, kansarka hunguriga hunguriga, iyo kansarka ganaca) kuwaas oo ku guuldareystay daaweynta caadiga ah;

3.Claudin 18.2 IHC wasakh wanaagsan;

4.Nolosha lafilayo> 12 todobaad;

Daaweynta C-T-Cell daaweynta shaqaalaynta

Marka lagu daro horumarka kor ku xusan ee horumarka cilmi baarista caafimaad, cosbitaalada waaweyn ee gudaha ayaa hada si firfircoon u sameynaya cilmi baarista CAR-T ee burooyinka kala duwan.

Shuruudaha bukaan-socodka: Da'da 18-80 sano jir, oo la filayo inay noolaato ugu yaraan 6 bilood (laga bilaabo dib-u-eegista hore ee qalabka illaa dhammaystirka daaweynta waxay qaadataa 5-6 bilood), guud ahaan xaalad wanaagsan, awood u leh inay kaligood noolaadaan.

Nidaamka dalabka ee qorista CAT T-Cell

1. Dib u eegis horudhac ah oo agabka: warbixinta cudurada, xogta baadhista sawirka hal bil gudaheed, warbixintii shaqada ee beerka iyo kelyaha ee dhawaa, soo koobida dheecaan dhawaan loo gudbiyay Waaxda Caafimaadka CancerFax;

2. La-tashi fool-ka-fool ah: Bukaanku laftiisu wuxuu u keenay dhammaan qalabka kiisaska isbitaalka tababarka qorista ee isbitaalka wajiga-ka-foolka ah (warbixinta kiisaska, soo-koobidda sii-deynta, filimka sawirka imaging);

3. Immuno histochemical detection: ogaanshaha unugyada burooyinka antigens EGFR, MUC1 iyo mesothelin, mid ka mid ah kuwaas oo si xoog leh u wanaagsan (muujin sare) ayaa codsan kara daaweynta CAR T-Cell.

Kahor imaanshaha daawaynta unuggu, burooyinka adag, oo ay ku jiraan adenocarcinoma gastric ee horumarsan iyo kansarka ganaca, ayaa inta badan lagu daweeyey qalitaan iyo daaweyn shucaac ah iyo kiimoterabi. Dhacdooyinka adenocarcinoma gastric ayaa lagu xisaabiyay 95% malignancies gastric malignancies, iyo kansarka ganaca ayaa ahaa buro halis ah oo caadi ah. Burada leh heerka ugu sarreeya, wakhtiga badbaadada dhexdhexaadka ah iyo heerka badbaadada 5-sano ayaa aad uga hooseeya burooyinka kale, oo loo yaqaan "boqorka kansarka".

Si kastaba ha noqotee, bukaanada badankood waxay leeyihiin soo noqnoqoshada maxalliga ah ama metastasis qalliinka ka dib. Intaas waxaa sii dheer, burooyinka noocan ah ee u nugul ma ahan kuwo u nugul shucaaca iyo daaweynta kiimikada. Sidaa darteed, iyada oo ku saleysan daaweynta caadiga ah ee hadda jirta, saameynta daaweynta ma fiicna, saadaalkuna aad ayuu u liitaa. Soo bixitaanka tallaalku wuxuu u keeni doonaa rajo badan iyo mucjisooyin badbaado waqti dheer ah bukaanno aad u horumarsan.

Waxaan si adag u aaminsanahay in ka dib marka la hirgaliyo nidaam xakameynaya difaaca jirka oo dhameystiran, dalku uu albaabka u furi doono habka difaaca jirka ee gacanta si looga faa'iideysto bukaanno badan oo kansar ah, sidoo kale wadankeena difaaca jirka ayaa sidoo kale ka mid noqon doona masraxa caalamiga.

Waxaa laga yaabaa inaad jeceshahay inaad akhriso: CAR T-Cell daaweynta Shiinaha

Su'aalaha la Weydiiyo ee ku saabsan CAR T-Cell therapy

Daaweynta unugyada Car-T ma la heli karaa? Waa maxay kansarka inta badan la daaweeyaa

A CAR-T cell immunotherapy has been ansixiyay by the US FDA for the treatment of leukemia and lymphoma. Si kastaba ha noqotee, daaweynta burooyinka adag wali lama ansixin waxayna hadda ku jirtaa tijaabooyin caafimaad

Unugyada Car-T ma daaweyn karaan kansarka caloosha ku dhaca?

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Ma jiraa tijaabo caafimaad oo lagu sameeyo unugyada Car-T ee kansarka caloosha?

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Bukaannada kansarka beerka ma ka qaybqaadan karaan tijaabooyinka CAR-T?

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Codso daaweynta CAR T-Cell

Codso Hadda