Waa maxay daaweynta CAR T-Cell?
Daaweynta T-Cell-ka Baabuurka, oo magaciisu buuxa yahay Chimeric Antigen Reptor T-Cell Immunotherapy,. Kani waa nooc cusub oo daawaynta unugyada ah oo la isticmaalayey sannado badan, laakiin la wanaajiyey oo keliya oo loo isticmaalay kiliinikada sannadihii u dambeeyey. Si la mid ah immunotherapy kale, mabda'a aasaasiga ah waa in la isticmaalo unugyada difaaca ee bukaanka u gaar ah si ay u nadiifiyaan unugyada kansarka, laakiin farqiga u waa in tani ay tahay daawaynta unug, ma daroogo.
Nidaamka daaweynta CAR T-Cell
1: Kala sooc unugyada difaaca T ee bukaanka kansarka.
2: Using genetic engineering technology to add a chimeric antibody that recognizes buro cells and activates T cells to kill tumor cells at the same time, T cells instantly turn into tall CAR-T cells. It is no longer an ordinary T cell, it is a “terrorist” T cell with GPS navigation, ready to find cancer cells and launch suicide attacks at the same time!
3: Dhaqanka in vitro, tiro badan oo unugyada CAR-T ah ayaa la ballaariyay. Guud ahaan, bukaanku wuxuu u baahan yahay balaayiin ama xitaa tobanaan balaayiin oo unugyo CAR-T ah (marka uu bato cabbirka jirka, unugyo badan ayaa loo baahan yahay).
4: Unugyada CAR-T ee la balaariyay waxaa lagu soo celiyaa bukaanka.
5: Si dhaw ula soco bukaanada, gaar ahaan falcelinta rabshada leh ee jirka maalmo ka hor (sababta gadaal ayaa laga sharixi doonaa), howshana dhamee.
Hagaajinta habka wax soo saarka unugyada
Sida loo soo saaro unugyo caalami ah oo CAR-T si loo yareeyo kharashka wax soo saarka waa caqabad weyn. Mid ka mid ah habka suurtogalka ah waa in laga helo unugyada T ee deeq-bixiyeyaasha, garaaca hidda-wadaha HLA ee unugyada, oo muujiya molecules HLA-ga aan caadiga ahayn si looga hortago aqoonsiga unugga dhexdhexaadinta ee dilaaga dabiiciga ah iyo lysis unug, taas oo soo saarta wax soo saarka guud ee T unuga. Intaa waxaa dheer, waxaa laga yaabaa inaanay lagama maarmaan ahayn in lagu dhex daro hiddo-wadaha CAR ee koromosoomyada unugyada T, maadaama muujinta ku-meel-gaarka ah ee CAR ee lagu beddelay RNA ay sidoo kale ka shaqeyso moodooyinka xayawaanka. Badbaadada dheeraadka ah, warbaahinta aan serum-ka lahayn ayaa lagula talinayaa.
FDA ayaa dhowaan soo saartay oo daabacday tilmaamo qabyo ah oo loogu talagalay alaabada daaweynta unugyada iyo hiddo-wadaha, mid ka mid ah oo u baahan soo saarayaasha inay go'aamiyaan tilmaamayaasha waxqabad ee unugyadan ama alaabada daaweynta hiddo-wadaha. Noocyada T ee hiddo ahaan wax laga beddelay, waxaa jira arrimo badan oo laga yaabo inay la xiriiraan waxqabadka, oo ay ku jiraan side hiddaha, xaaladaha dhaqanka, Qaab dhismeedka CAR, nooca unugyada, iyo saamiga nooca unugga. Waqtiga xaadirka, tilmaamaha ugu fudud ee waxqabadka waa tirada unugyada CAR +. Si kastaba ha noqotee, nooca saxda ah ee unugga ayaa si isku mid ah muhiim ugu noqon kara waxqabadka. Tusaale ahaan, noolaanshaha muddada-dheer ee unugyada xusuusta dhexe, unugyada CD8 +, waxay noqon karaan tilmaame waxqabad. Inta badan cilmi-baarayaashu waxay hadda diiradda saaraan unugyada T ee laga soo qaatay dhiigga durugsan. Baarayaasha qaarkood waxay adeegsadeen CAR jiilka labaad si ay ugu gudbiyaan unugyada dilaaga dabiiciga ah.
Waxaa laga yaabaa inaad jeceshahay inaad akhriso: CAR T-Cell daaweynta Hindiya
Faa'iidooyinka daaweynta CAR T-Cell ee daaweynta cudurada dhiig baxa
Shantii sano ee la soo dhaafay, waxtarka wanaagsan ee CAR-T ayaa si joogto ah u noqday cinwaannada qaar ka mid ah xarumaha cilmi-baarista. Sababtoo ah waxaa jira waxyaabo badan oo antigen ah oo loo yaqaan xuubka unugyada dhiigga, waana sahlan tahay in la helo leukocytes iyo unugyada T si dabiici ah u ah xubnaha dhiigga (sida dhiigga, dhuuxa lafta, iyo qanjidhada), unugyada CAR-T ayaa marka hore loo isticmaalaa in lagu daweeyo. leukemia xun. Yaaban.
CAR-T cells are also the most used clinical trials for hematological malignancies. The results of these clinical trials indicate several key factors that may affect the efficacy of CAR-T cell therapy. For example, although all diseases can express CD19, Lymphoblastic lymphoblastic leukemia appears to have a higher response rate than chronic lymphocytic leukemia or indolent lymphoma. The reasons may include patients with lymphoma have T cell defects, tumor microenvironment inhibition, previous treatment, the patient’s age and T cell activity and components (such as the ratio of CD4: CD8, the content of regulatory T cells). The tumor microenvironment may also affect the function of CAR-T cells to dissolve tumor cells. By analyzing CAR-T cells isolated from tumor tissue, they found that they express PD-1, so the therapeutic effect may be affected by PD-L1. Checkpoint blocking technology can increase T cell viability. Application of lymphatic attrition and injection of lymphokines can support the in vivo expansion and survival of imported T cells.
Waa muhiim in la fahmo sifooyinka muhiimka ah ee dhaqdhaqaaqa unugyada CAR-T. Muujinta CAR ee dusha unugyada shaki la'aan waa muhiim. Marka labaad, unugyo CAR-T oo ku filan waa in lagu ogaan karaa dhiigga ka dib tallaalka. Unugyada CAR-T waxaa lagu ogaan karaa falcelinta silsiladda polymerase iyo cytometry socodka. Ma cadda waxa qiyaasta ugu yar ee unugyada CAR-T loo baahan yahay si ay waxtar u yeeshaan. Haddii unugyada CAR-T si wax ku ool ah loo ballaariyo gudaha vivo, markaa qadar yar oo ah unugyada CAR-T ayaa wali soo saari kara saameyn wanaagsan. Marka la eego kakanaanta soo saarista unugyada CAR-T, aad bay u soo jiidataa in lagu gaaro saameyn daweyn oo ah qiyaas yar oo unugyo ah. Shaki kuma jiro in unugyada dibadda laga keeno ay tahay inay badbaadaan waqti ku filan. Iyada oo ku saleysan kinetics ee nadiifinta unugyada burooyinka ee la arkay, unugyada la tallaalay waxay u baahan yihiin inay ku noolaadaan vivo ugu yaraan dhowr bilood. Dhanka kale, haddii unugyada CAR-T kaliya loo isticmaalo daawaynta ku-meel-gaadhka ah ee ku-tallaalidda dhuuxa lafta, markaa waxay u baahan karaan oo keliya inay socdaan dhowr toddobaad. Ma jirto daraasad caafimaad oo aan kala sooc lahayn oo caddaynaysa in unugyada CAR-T ay bedeli karaan tallaalka dhuuxa lafta. Laakiin ugu yaraan bukaannada aan ku habboonayn beddelidda dhuuxa lafta waxay heli karaan beddelka unugyada CAR-T.
Toxicity and adverse reactions mainly include cytokine release syndrome, macrophage activation syndrome, hemophilic qanjiro and B cell hypoplasia. Calaamadaha sii deynta Cytokine is often accompanied by high levels of IL-6 secretion and leads to macrophage activation syndrome. Although it can be clearly assumed that CAR-T cells can directly kill tumor cells, it is not completely clear which cells produce a large number of cytokines, especially IL-6 (a key factor for toxic response). It is also unclear whether general immunosuppression of anti-cytokine antibodies or steroid hormones can affect anti-tumor responses. IL-6 may be produced by dead B cells, dead tumor cells, or macrophages recruited to lyse tumor cells. It is still unclear whether the severity of cytokine release syndrome or macrophage activation syndrome is related to the anti-tumor effect. The relatively rare adverse reactions include slow response, epilepsy, aphasia, changes in mental state, etc. These are reversible. Macrophage activation syndrome is often associated with neurological toxicity. B cell hypoplasia is the expected result of CD-19 daaweynta la beegsaday and can be used as an indicator of the survival and effectiveness of CD-19 targeted CAR-T cells in vivo. B cell hypoplas
ia waa lagu duri karaa glycinin oo ah daaweyn dheeri ah. Daawaynta B-cell hypoplasia oo joogto ah, xitaa iyada oo lagu daweynayo daaweynta, waxay u horseedi kartaa halista sii kordheysa ee cudurka. Unugyada B way soo kaban karaan ka dib markay unugyada CAR-T ku dhex baaba'aan jirka, sidaas darteed bukaanku waxay mar kale heli karaan unugyada CAR-T. Maaddaama bukaanno badan ay helaan daaweynta unugga CAR-T, cilmi-baarista bukaan-socodka waa inay diiradda saaraan daraasadda fal-celinta sunta iyo hababka maareynta, oo ay ku jiraan xannibaadda cytokine, steroids, iyo waqtiga ugu habboon iyo qiyaasta kaabista borotiinka.
Sababtoo ah sunta weyn ee unugyada CAR-T, cilmi baarayaashu waxay sidoo kale isku dayeen xeelado ay ku midoobaan hiddo-wadayaasha is-miidaaminta unugyada ama daminta muujinta hidda-wadaha. Si kastaba ha noqotee, wali way adagtahay in lagu daro nidaamka hiddo-wadaha ismiidaaminta ee dhammaan unugyada CAR-T, maxaa yeelay nidaamyo badan oo hidde-wadayaal is-miidaamin ah ayaa difaaca jirka ah (tusaale ahaan, fayraska herpes simplex oo muujiya thymus kinase) ama daawooyinka keena ismiidaaminta waa in lagu sameeyaa faleebada. Intaa waxaa sii dheer, T-cell homing waxaa lagu beddeli karaa muujinta ku-meel-gaadhka ah ee qabtayaasha kiimikada ama xannibaadda dawooyinka ee daawooyinka loo yaqaan 'chemokine receptors' ayaa loo isticmaali karaa istiraatiijiyad lagu xoojinayo waxtarka loona yareeyo sunta.
Rajada xiisaha leh ee daaweynta CAR T-Cell
There are two main obstacles in expanding the application of CAR-T cells beyond B-cell malignancies: finding new targets and mass production. Potentially promising targets include CD30 (for the treatment of Hodgkin’s disease and fungoides mycosis), immunoglobulin Gκ light chain (for the treatment of B-cell leukocytes), CD33 and Lewis-Y (acute myeloid leukemia), CD123 and CD44v6 (Acute myeloid leukemia and myeloma), CD19 (B cells), CD23, and ROR1 (chronic lymphocytic leukemia). New targets under study include BCMA, CD70, CD74, CD138 and CS1 (see table below). Currently, pharmaceutical companies, biotechnology companies, universities, and cooperative organizations are conducting CAR-T cell research. This is an exciting period for the treatment of all hematological malignancies; ten years ago, few people expected that the hope of modifying gene therapy would be realized by CAR-T cells for the treatment of hematological malignancies.
Faa'iidada Kansarka waa degelkii ugu horreeyay ee gudaha ah ee sameeya ogaanshaha iyo la-talinta daaweynta kansarka adduunka. Waxay la shaqaysaa in ka badan 30 machadyada daawaynta iyo ogaanshaha kansarka caalamiga ah iyo in ka badan 300 khubaro ah gudaha iyo dibaddaba si ay u bixiyaan la-talinta khabiirka oncology iyo la-talinta bukaannada gudaha si ay uga caawiyaan bukaannada si ay u helaan baaritaanka ugu horumarsan ee Hiddaha, daawooyinka, tignoolajiyada iyo daaweynta tijaabada caafimaad. la habeeyey oo la gaar yeelay.
