Jikin ku yana da nau'o'in nau'in jini. Ɗaya daga cikin irin, lymphocyte , ya zo ne a cikin manyan nau'i biyu: B-cell da T-cell. A nan, a cikin mahallin maganin ciwon daji, muna da damuwa da wannan nau'i na biyu, T-cell.
Don haka, menene mai karfin maganin antisigen antigon (CAR) T-cell farrapy? A taƙaice, yana da wani maganin da zai iya yin amfani da kwayoyin halittar T wanda ya fi kyau a gane da kuma ci gaba da ciwon ciwon daji a ciki.
Yana daya daga cikin nau'in immunotherapies iri-iri da ake bincika. Idan kuna da sha'awar ilimin kimiyyar kimiyyar kimiyya a cikin irin wannan farfadowa, cikakkun bayani game da yadda tsarin na CAR T-cell ya ba da wannan hangen zaman gaba.
A nan, mayar da hankali shine akan "maganin kwantar da hankula" da sauran cututtuka irin wannan da ke aiki ta hanyar T-kwayoyin jikinsu - "sassan soja" na jiki-don yaki da ciwon daji ta hanyar ganewa da kuma kai hare-haren kwayoyin tumo. Wasu ƙwayar cutar ciwon daji da ke amfani da jikin T-jikinka an riga an yarda, kuma ana sa ran wasu za su biyo baya nan da nan.
Shirya hanya tare da Jiyya marasa lafiya
Tinkaya tare da tsarin jikinka na jikinka don kokarin magance ciwon daji ba cikakke ba ne. A gaskiya ma, akwai misalai na irin wannan maganin (wanda ya mayar da hankali ga amsawar T-cell) wanda ya riga ya sami izinin FDA: sipuleucel-T, ipilimumab, da blinatumomab, alal misali.
Jiyya | Kwayar cutar Cancer | Ba da izini ba |
Sipuleucel-T (Shari'a) | Wasu lokuta na ciwon daji na ciwon gurgu |
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Ipilimumab (Yervoy) | Wasu lokuta na m melanoma fata ciwon daji |
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Blinatumomab (Blincyto) | Rushewa ko ƙyama B-cell precursor m lymphoblastic cutar sankarar bargo (ALL) a cikin manya da yara |
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Ɗaya daga cikin su, sipuleucel-T, sauti kamar sauti na TT-cell ne a cikin cewa yana amfani da kwayoyin jikinku wanda aka tattara daga jini gaba ɗaya sannan sannan aka sarrafa shi a cikin dakin gwaje-gwaje; an kunna su kuma an sa su zama mafi dacewa da kwayoyin tumatir, sa'an nan kuma su koma cikin jini kamar yadda farfadowa.
Sipuleucel-T an dauke shi "maganin rigakafi", ko kuma "immunotherapy cellular autologous," amma ba hanyar T-cell ta CAR ba tun lokacin da ake horar da kwayoyin halittar ba tare da amsawa ba, maimakon zama a jiki don magance ƙwayoyin tumatir. .
Masu hana masu bincike na ban mamaki kamar su ipilimumab (sama) suna aiki tare da nau'ikan tsarin da ke cikin rigakafi na "yin amfani da takalmin," ko kuma "kaddamar da iskar gas" a jikin tsarin jiki, don kokarin yin amfani da kare lafiyarka daga ciwon daji. Ipilimumab misali daya ne kawai na maganin da ke aiki a wannan hanya. Wani misali na mai hana magungunan dubawa shi ne pembrolizumab (Keytruda), wanda ya kera wani "kashe-kashe" don t-jikin T, wanda ake kira PD-1.
Tsarin Rikicin CAR-T: Gaskiya "Rayayyun Kwayoyi"
Kwayoyin cutar ta CAR-T, duk da haka, suna da alaƙa da kansu. Ana fitar da kwayoyin T daga jikinka, an tsara su ta hanyar halittar jiki don ganewa da kuma kashe kwayoyin tumo, sa'an nan kuma sake gabatar da su a matsayin farfadowa mai rai. Za a iya yin amfani da kwayoyin halitta kuma a girma a cikin 'yan kwanaki 21 sannan kuma an mayar da su cikin jini.
Tsarin kwayar cutar CAR T ba nau'i ne da za a yi amfani da ita ba kafin kokarin wasu jiyya-akalla, ba a yanzu ba. Wadannan sababbin jiyya kullum sun fito ne daga mummunan gaskiyar cewa, ga marasa lafiya da cututtuka, maganin ciwon daji na al'ada, ciki har da tiyata, chemotherapy, da kuma radiationrapy, lokuta suna ba da tasiri sosai.
Saboda haka, har ya zuwa yanzu, hanyoyin maganin cutar ta CAR-T kawai suna samuwa ga marasa lafiya da suka shiga cikin gwaji, kamar yadda ake kula da maganin a binciken Amurka, amma wannan zai iya canzawa nan da nan. Cutar ta CAR-T za ta iya zama FDA ta yarda da samuwa a waje da gwajin gwaji a cikin 2017-2018.
A taƙaitaccen jerin sunayen manyan 'yan takarar da ake ci gaba da gina jiki.
CTL019 (tisagenlecleucel) by Novartis
CTL019 wani ƙwararren antigen receptor (CAR) mai ƙwayar cuta ta CD-ROM (CAR) wanda ke da ƙwayar T-cell.
Bari farawa ta hanyar ɓarke kalmar da ta gabata: CD19 wani ƙwayoyin kwayoyin halitta a kan wasu kwayoyin da ke dauke da kwayoyin halitta B, kuma waɗannan kwayoyin zasu iya zama tushen wasu cutar sankarar bargo da lymphoma .
Kashi ɗaya na CTL019 ya kawo jinkirin da zai yiwu kuma zai iya warkar da mu (ba mu sani ba tukuna) ga yawan marasa lafiya a cikin binciken da suke gudana daga cikin zaɓin magani.
Ga alamar cututtuka na abin da CTL019 ke la'akari a halin yanzu:
- CTL019 ya karbi FDA Breakthrough Nazarin farfadowa don kula da marasa lafiyar marasa lafiya tare da sake yaduwa / kyamarar babban lymphoma B-cell (DLBCL). (Lymphomas an rarraba su a cikin kungiyoyi guda biyu: Hodgkin da wadanda ba Hodgkin. Mafi yawan ilmin lymphoma ba na Hodgkin shine DLBCL).
- CTL019 kuma ya yarda don kula da nakasawa ko nakasa lafiyar yara da marasa lafiya marasa lafiya tare da B-cell lymphoblastic cutar sankarar bargo (ALL).
CTL019 sun samu kuri'u (10-0) na amincewa da amincewa daga kwamiti na Kwararrun Magunguna ta FDA, ma'ana cewa abubuwa suna sa ran samun nasara. Novartis yana nufin CTL019 da za a yarda da shi don magance ƙwayar cutar B-cell ALL a cikin yara da matasa marasa lafiya. Cutar sankarar bargo ne lambar daya ciwon daji na yara, kuma ALL shine nau'i na kowa, wanda ke da alhakin kashi 25 cikin dari na ƙwayar cutar yara. Akwai nau'o'in ALL, ciki har da B-cell ALL da T-cell ALL, kuma subtypes cikin iya ɗaukar nasu prognoses.
CTL019 a halin yanzu an yi la'akari da fifiko da fifiko kuma dacewa da amincewar lokaci zai zama saitin farko na CAR-T don samun samuwa. Tsarin T-kwayar cutar ta CAR zai samuwa ne kawai don ƙananan yara da matasa waɗanda cutar sankarar bargo ba ta amsawa ba. Wadannan marasa lafiya suna da matsala mara kyau, amma a cikin gwajin gwajin gwajin gwaji a cikin kusan kasashe goma sha biyu, kashi 83 cikin dari na marasa lafiya sun shiga gafartawa. Bayan shekara guda, kashi biyu cikin uku sun kasance haka.
Saboda maganin ya lalata ƙwayoyin leukemic B kawai amma har da lafiya, iri-iri masu fama da kwayar cuta, marasa lafiya suna buƙatar magani don kare su daga kamuwa da cuta. Suna karɓar infusions na rigakafi globulins kowane watanni kamar yadda ma'auni m.
Ɗaya daga cikin cututtukan da yafi amfani da shi shine ana kiran ciwon sikila na cytokine, wanda zai haifar da babban zazzaɓi da kuma irin alamun bayyanar cututtuka cewa a wasu lokuta zai iya zama mai hatsarin gaske cewa mai haƙuri ya ƙare cikin kulawa mai tsanani. Sauran damuwa mafi girma shine ƙananan ƙwayoyin cuta, wanda zai haifar da rikice rikice ko rikicewar ƙwaƙwalwar ƙwaƙwalwa.
Don kokarin tabbatar da lafiyar lafiyar, Novartis ba yana shirin kullun kayan aiki, tare da maganin miyagun ƙwayoyi da aka tura kamar yadda ya kamata. Kamfanin maimakon maimakon haka zai sanya cibiyoyin likita 30 zuwa 35 don gudanar da magani. Yawancin su sun shiga cikin gwajin gwagwarmaya, kuma duk sun sami horo sosai.
Ciloleucel ta Axicabtagene ta Kite Pharma
Bisa ga Santa Monica, California, Kite Pharma wani kamfani ne wanda ke mayar da hankali kan hanyoyin kwantar da hankulan kwayar cutar ta CAR da kuma T-cell. Kite yana tasowa ne a cibiyar kiwon lafiya ta CAR ta kira axicabtagene ciloleucel, wanda yanzu yake a cikin bita a Amurka don magance marasa lafiya tare da mummunan ƙwayar lymphoma ba Hodgkin (NHL). Marasa lafiya tare da mummunan NHL na fuskantar mummunar ganewa tare da kawai kashi 50 cikin 100 na rayuwa na watanni shida. Wannan yana nuna muhimmancin likita na gaggawa ga marasa lafiya.
Kamar CTL019, axicabtagene ciloleucel yana ci gaba da cike da antigen CD19, wani furotin da aka bayyana a kan tantanin halitta na lymphomas da leukemias na B-cell. Ana amfani da ƙwayoyin T na masu haɗin gwiwa don bayyana wani mai karɓar maganin antigetan (CAR) don ƙaddamar da CD din antigen.
A cikin ci gaba da maganin maganin miyagun ƙwayoyi, axicabtagene ciloleucel yana da irin wannan labarun zuwa CTL019, a cikin abin da aka mayar da hankali a kan malignancies wanda ke da asalin B, amma B cell ALL ba ya zama wani ɓangare na ci gaba na ƙwarewa ba. a wannan lokaci.
Ga alamar cututtukan cututtuka na abin da ake la'akari da axicabtagene ciloleucel a halin yanzu:
- An ba da izinin cike da ciwon daji na Breakthrough Farignation don yada manyan lymphoma B-cell (DLBCL), lymphoma follicular (TFL), da kuma magunguna na B-cell lymphoma (PMBCL) na FDA da kuma Magunguna na Farko (PRIME). DLBCL a cikin EU.
Ana yarda da karbar wannan bayani daga ZUMA-1 Farawa 2 na gwaji wanda ya hadu da asali na farko na tsarin amsawa (ORR) da aka rubuta bayan bayanan guda guda na axicabtagene ciloleucel da kashi 82 (p <0.0001). A cikin watanni 8.7, kashi 44 cikin 100 na marasa lafiya suna ci gaba da amsawa, wanda ya hada da kashi 39 cikin dari na marasa lafiya a cikin cikakken amsa (CR).
Abubuwa masu rikitarwa na yau da kullum sun hada da raguwa daga cikin kwayoyin lafiya wanda ke yaki da kamuwa da cuta da kuma taimakawa jini don yin gudanarwa. Kamar yadda CTL019, daya daga cikin cututtukan da yafi amfani da shi shine ana kiran ciwon sikila na cytokine, wanda ke haifar da babban zazzabi da kuma irin alamun bayyanar cututtuka cewa a wasu lokuta na iya zama mai hatsarin gaske cewa mai haƙuri ya ƙare cikin kulawa mai tsanani. Hanyoyin cututtuka na iya haifar da rikice rikice ko rikicewar ƙwaƙwalwar ƙwaƙwalwa. Akwai mutuwar mutane uku a duk lokacin da aka yi rajistar rajistar ba saboda rashin ci gaban cutar ba, wanda wasu abubuwa biyu suka kasance suna da dangantaka da axicabtagene ciloleucel. Bugu da ƙari, ana sa ran ci gaba da ƙwayar magungunan wadannan kwayoyi ne tare da taka tsantsan.
GoCAR-T, Kwararre ga Tumatir Tumatir da Bellicum Pharmaceuticals
Houston, Texas, mai suna Bellicum Pharmaceuticals, Inc., na da 'yan takarar miyagun ƙwayoyi waɗanda suka hada da BPX-601 (Candidar GoCAR-T, don ƙwayar ciwon daji, wanda aka tsara tare da sauyawa mai kunnawa iMC don inganta ingantaccen aiki, lokaci na), da BPX-701 (high -affinity TCR dan takara, don ƙwayoyin ciwon daji , wanda aka tsara tare da sauya yanayin CaspaCIDe, lokaci na).
Don haka, menene duk abin yake nufi? Ainihin haka, wannan rukuni na aiki a kan sake amfani da fasahar T-cell ta CAR don haka zai iya bawa likitancin karin iko kan amsa T-cell. An tsara ƙwayoyin GoCAR-T don a kunna su kawai idan an bayyana su zuwa duka kwayoyin cutar kanjamau da kuma wakili da ake kira rimiducid. Sabili da haka, ya kamata, likitan zai iya sarrafa ikon yin amfani da ƙwayoyin na CAR-T ta hanyar daidaita tsarin jimillar rimiducid, amma kashewar salula zai kasance a halin da ake ciki.
Sauran 'yan takara
Juno wani kamfani ne wanda ke mayar da hankali a kan JCAR017, na'urar samfur ta CAR-T wanda ke sa ran CD19. Juno yana neman samun JCAR017 a kasuwa a farkon 2018 don NHL. Kamfanin ya rabu da Celgene a cikin wadannan kokarin.
ZIOPHARM Oncology na da samfurin CD19 da ke aiki kuma yana aiki ne a kan ƙwayoyin CDT-CD33 na musamman na CD-ROM don sake komawa da cutar sankarar bargo (AML). NantKwest shi ne kamfani na immunotherapy kan mayar da hankali ga yin amfani da kwayoyin cutar kisa (NK) don magance ciwon daji, cututtuka, da cututtukan ƙwayoyin cuta.
Kamfanin NK na kamfani ya tsara don haifar da mutuwar kwayar cutar ta hanyar ciwon daji ko kamuwa da kwayar cutar ta hanyar sauye-sauye daban-daban na kashe-kashe ta hanyar yin amfani da kwayoyin NK kunnawa (aNK); kisan kare dangi da aka kashe ta hanyar amfani da haNKs, kuma aka kashe kashe ta hanyar amfani da taNKs.
Kalma Daga
Wasu daga cikin sabbin sakamakon da aka samu daga cibiyar kiwon lafiya na CAR-T sun yi farin ciki sosai, suna ba da sababbin hanyoyin kwantar da hankalin marasa lafiya wadanda ba su da irin wannan zaɓin kafin su kasance. Akwai kuma rashin gazawa, duk da haka, kuma akwai wani matsala na warware matsalolin da za su iya yin wadannan maganin asibiti a matsayin tasiri sosai tare da ƙananan yawan guba.
Yayinda masu bincike suka koyi game da maganganun da ba'a samu ba a cikin wadannan maganin, da kuma tasiri akan mummunan makirci, wani bayyani mai zurfi game da hadarin da wadata ya kamata ya fito.
> Sources:
> Wang M, Yin B, Wang HY, Wang RF. Kasuwa na yau da kullum a cikin ciwon T-cell na ciwon immunotherapy. Immunotherapy . 2014; 6 (12): 1265-1278.
> Bhoj VG, Arhontoulis D, Wertheim G, et al. Tsayawa da kwayoyin cutar plasma da dogon lokaci da maganin kare hakkin dan Adam a cikin mutane da ke amsawa da maganin CD-T-cell na TT-CD. Jinin jini. 2016; 128 (3): 360-370.
> Kite ya karbi Dokar Abinci da Drug da Amurka ta Yi Mahimmanci ga Axicabtagene Ciloleucel. http://ir.kitepharma.com/releasedetail.cfm?releaseid=1028075 An shiga Yuli 2017.
> Morris EC, Stauss HJ. Tabbatar da matakan T-cell receptor gene far for hemignlogic malignancies. Jinin jini . 2016; 127 (26): 3305-3311.
> Park JH, Geyer MB, Brentjens RJ. CD19-ƙaddamar da ƙwayoyin magani na CAR T-cell for malignancic malignancies: fassara fassarar sakamakon asibiti zuwa yau. Jinin jini . 2016; 127 (26): 3312-3320.