Mumuviri wako ane marudzi akasiyana emasero machena eropa. Mhando imwe, lymphocyte , inouya mumhando miviri mikuru: B-cell uye T-cell. Pano, mumamiriro ekurapa kwekenza, isu tinonyanya kufunga nezvechipiri chechipiri, T-cell.
Saka, chimeric antigen receptor (CAR) T-cell therapy? Muchidimbu, iyo inopedza maitiro ekugadzirisa maitiro anogadzira zvirongwa zvako zvekuti T-seli dzive nani pakuziva nekurwisa kenza mukati.
Icho chiri chimwe chezvizhinji zvemiviri yemunyanzvi iri kuongororwa. Kana iwe uchifarira biotechnology seri kwechirwere ichi, pane tsanangudzo yakajeka yekuti CAR T-cell therapy inoshandisa sei iyo maonero.
Pano, chinonyanya kukosha pane "mararamiro anorarama" uye mamwe marapirwo akafanana anoshanda kuburikidza neT-seli-muviri wako "masimba emasikirini" -kurwisa kenza nekuziva nekurwisa tumarara masero. Mimwe mishonga yemukenza inoshandisa T-seli yako yomuviri yakatogamuchirwa, uye vamwe vanotarisirwa kutevera nekukurumidza.
Kugadzira Nzira Yokurapa Kwokuchengetedzwa Kwemaviri
Kufungidzira muviri wako mumuviri wako kuedza kurwisa kenza hakusi itsva zvachose. Zvechokwadi, kune mienzaniso yemishonga yakadai (iyo inotarisa paT-cell response) yakatove yakagamuchira FDA kugamuchirwa: sipuleucel-T, ipilimumab, uye blinatumomab, somuenzaniso.
Kurapa | Cancer Type | Immune System Action |
Sipuleucel-T (Zvimwe) | Zvimwe zviitiko zvekenza yepamusoro yeprostate |
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Ipilimumab (Yervoy) | Zvimwe zviitiko zvehutachiona hwechirwere chinorwarisa |
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Blinatumomab (Blincyto) | Kudzorerwa kana kukanganisa B-cell precurse acute lymphoblastic leukemia (ALL) muvanhu vakuru nevana |
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Mumwe wavo, sipuleucel-T, inonzwika zvakadai seC CAR T-cell therapy pakuti inoshandisa masero ako emumunondo anotanga kuunganidzwa kubva muropa rimwechete uye ozoshandurwa mu laboratori; izvo zvinoshandiswa uye zvakaitwa kuti zvive zvakanyanya kugamuchira kumarara kwemasero, ndokubva vashandura zvakare muropa rega semishonga.
Sipuleucel-T inofungidzirwa se "autologous vaccine," kana "autologous cellular immunotherapy," asi, kwete CAR-T-cell therapy sezvo masero ezvirwere zvemusununguri ari kudzidziswa kupindura, panzvimbo yekugadzirisa maitiro evanhu kuti vapindure nemarara .
Immune checkpoint inhibitors yakadai sepilimumab (pamusoro) inoshanda nemaitiro ako ezvirwere zve "immune system" eku "kushandisa mabheki," kana kuti "kurova mafuta" mumuviri wemuviri, kuti uedze kuedza kudzivirirwa kwako nekenza. Ipilimumab inongova muenzaniso mumwe chete wemishonga inoshanda nenzira iyi. Imwe muenzaniso wekudzivirira zvirwere mumuviri inhibitor ndeye pembrolizumab (Keytruda), iyo inosanganisa "kuvhara" kweT-cells, inonzi PD-1.
CAR-T Muchirapa Muchidimbu: Chokwadi "Mishonga Inorarama"
CAR-T zvidzidzo zvemasero, zvisinei, zviri pachena kuti ivo pachavo vakasiyana. T-masero anotorwa kubva mumuviri wako, maitiro akarongeka kuti aone zviri nani uye auraye masero emuviri, uye anobva ataurwa sehupenyu hwehutano. Masero anogona kuumbwa uye kukura mumashoma semasvondo makumi maviri nemaviri uye ipapo anonyorerwa zvakare muropa.
KANA T-cell therapy haisi iyo nzira yerapi inogona kushandiswa isati yaedza mamwe maitiro-zvisinei, kwete ikozvino. Mishonga iyi mitsva inowanzobuda kunze kwechokwadi chinosuruvarisa kuti, kune varwere vane nguva yekupedzisira-chirwere, mishonga yekenza yemagariro, kusanganisira kuvhiyiwa, chemotherapy, uye remishonga inonzi radiation, kazhinji inopa kupa zvishoma kushanda.
Saka, kusvika ikozvino, CAR-T zvidzidzo zvekare zvinowanikwa chete kune varwere vakanyoresa mumakirini emakiriniki, sekurapa kunoonekwa sekuongorora muU.S., asi izvi zvinogona kuchinja munguva pfupi. Chikoro-T chechirwere chemasero chinogona kuva FDA chakagamuchirwa uye chinowanikwa kunze kwekuongororwa kwekliniki pasina 2017-2018.
Tsanangudzo shomanana yevamwe vakakosha zvikuru varikugadzirwa kwekliniki inotevera.
CTL019 (tisagenlecleucel) neNovartis
CTL019 iCD19-specific chimeric antigen receptor (CAR)-yakabatwa neT-cell therapy.
Ngatitange nokudhinda mutsetse wakapfuura: CD19 imorekemu kune mamwe masero emunodzi anonzi B-cells, uye aya masero anogona kuva mhando dzemamwe marudzi eukemia uye lymphoma .
Chirwere chimwe chete che CTL019 chakaunza kukonzera kwenguva refu uye zvichida kurapwa (isu tisingazivi) kune vakawanda varwere mune zvidzidzo vaive vachibuda kunze kwekusarudzwa kwemishonga.
Heino kukwira-kwezvirwere izvo CTL019 iri kuonekwa iye zvino:
- CTL019 yakagamuchira FDA Breakthrough Therapy mazita ekurapa kwevarwere vakura vakadzoka zvakare / kukanganisa zvikuru B-cell lymphoma (DLBCL). (Mishonga yemakumbo inowanzoiswa mumapoka maviri evanhu: Hodgkin uye kwete Hodgkin. Nyaya yakanyanya kufanana yeHodgkin lymphoma ndiyo DLBCL).
- CTL019 inobvumirwawo kurapwa kwekudzoka zvakare kana kuratidzira vana vevana uye vechidiki vakura varwere vane B-cell acute lymphoblastic leukemia (ALL).
CTL019 yakagamuchirwa chisarudzo chisina kubvumirana (10-0) chebvumirano kubva kune FDA's Oncologic Drugs Advisory Committee, zvinoreva kuti zvinhu zvinotarisira kuvimbiswa kwekugamuchirika kwayo. Novartis iri kutarisira CTL019 kuti inobvumirwe kurapwa kwekudzoka zvakare kana kusagadzikana B-cell ALL muvana uye vaduku vakura varwere. Leukemia ndiyo nhamba yemwana wekenza, uye ALL ndiyo inonyanya kufanana nayo, inotarisirwa kumapfumbamwe 25 muzana yeukondombera hwehuduku. Kune marudzi akasiyana eYOSE, kusanganisira B-cell ALL uye T-cell ALL, uye subtypes mukati mazvo vanogona kutakura mavara avo.
CTL019 iye zvino iri pasi pekuongororwa kwepamusoro uye kugamuchirwa kwenguva yakakodzera kwaizoita kuti yekutanga CAR-T cell therapy ivepo. IC CAR T-cell kurapa ingangowanikwa chete nechechi duku yevana nevechidiki vane ruzivo rwemaperembudzi vasingatauri kutarisirwa. Vaya varwere vanowanzova nehutachiona husina kunaka, asi mukuedzwa kukuru kwekuedza kurapwa mune inenge nyika gumi nemaviri, 83 muzana yevarwere vakapinda mukuregererwa. Gore rakatevera, zviviri zvezvitatu zvakaramba zvakadaro.
Nemhaka yokuti kurapwa kunoparadza kwete chete chirwere cheB-seli asiwo hutano hwakanaka, huri kurwisa hutachiona, varwere vanoda kurapwa kuti vavadzivirire kubva kune utachiona. Vanogamuchira kuvhiringidzika kwemaglobulbulin mwedzi mishoma mishoma sechidziviriro chekudzivirira.
Chimwe chezvinhu zvinowanzovhiringidza chinonzi cytokine release syndrome, chinokonzera high fever uye zvirwere zvakadai sezvirwere zvinenge zvichingova zvine ngozi zvokuti murwere anopedzisira ari mune zvakanyanya kutarisira. Icho chikuru chinoshushikana neurotoxicity, iyo inogona kuguma nekuvhiringidzika kwenguva pfupi kana kuti inogona kuuraya uropi huputi.
Kuedza kuvimbisa kuchengeteka kwevarwere, Novartis haasi kuronga chimiro chekugadzirwa kwechigadzirwa, nemishonga inokwidza zvakanyanya uye nechisimba sezvinobvira. Iyo kambani panzvimbo payo ichaisa mapurisa makumi matatu kusvika kune makumi matatu ekurapa kurapwa. Vakawanda vavo vakapinda muchirongwa chechipatara, uye vose vakawana kudzidziswa kwakakura.
Axicabtagene Ciloleucel naKite Pharma
Kubva kuSanta Monica, California, Kite Pharma ikambani inotarisa kuCAR uye T-cell receptor inoshandiswa masero epera. Kite iri kusimbisa CAR T-cell therapy inonzi axicabtagene ciloleucel, iyo ikozvino iri pasi pekuongororwa kwepamusoro muUnited States pakurapa kwevarwere vane kukanganisa kwechisimba kwete yeHodgkin lymphoma (NHL). Varwere vane chirwere chisingaiti NHL vanotarisana neshoko rakashata ne 50% chete mukana wekupona mwedzi mitanhatu. Izvi zvinotsanangura kudiwa kwekukurumidzira kwechiremba kwevarwere ava.
Kufanana neC CTL019, axicabtagene ciloleucel inosanganisa antigen CD19, puroteni inoratidzwa muchitokisi che B-cell lymphomas uye leukemias. Mumiririri T ane masero anogadzirirwa kuratidza chimeric antigen receptor (CAR) kutarisa antigen CD19.
Mukuvandudza zvinodhaka uye kugamuchirwa, axicabtagene ciloleucel ine purogiramu yakafanana kune yeCCTL019, pakuti iyo inotarirwa mumatambudziko ane B-cell yakabva, asi B cell ALL haiiti sechikamu chekuwedzera kwechipatara panguva ino.
Hezvino kunyura-kwezvirwere izvo axicabtagene ciloleucel iri kuonekwa iye zvino:
- Axicabtagene ciloleucel yakapiwa chirongwa cheBreatthrough Therapy Designation mamiriro ekupararira kweB-cell lymphoma (DLBCL) yakawanda, yakashandurwa follicular lymphoma (TFL), uye inonzi primary-medial B-cell lymphoma (PMBCL) neUSA FDA uye Priority Medicines (PRIME) DLBCL muUnited States.
Kugamuchirwa seChitthrough Therapy neDaDa kunotsigirwa nemashoko kubva kuZUMA-1 Phase 2 muedzo iyo inosangana nepfungwa yekupedzisira yechinangwa chekupindura zvinokwana (ORR) yakanyorwa mushure mekukanganiswa kwe axicabtagene ciloleucel ne 82 muzana (p <0.0001). Pakati pekutsvaga kwemukati kwemwedzi 8.7, 44 muzana yevarwere vaive nekupindurwa kwakapfuurira, izvo zvaisanganisira 39 muzana yevarwere mukupindura zvakakwana (CR).
Zviitiko zvinowanzovhiringidza zvinosanganisira kupera kwemasero ane utano anorwisana nehutachiona uye anobatsira ropa kuvhara. Sezvakaita CTL019, chimwe chezvinhu zvinowanzovhiringidza chinonzi cytokine release syndrome, chinokonzera high fever uye zvirwere zvakadai sezvirwere zvinogona kunge zvisingakonzereri kuti murwere anopedzisira aine chirwere chakasimba. Encephalopathy inogona kukonzera kukanganisika kwenguva pfupi kana kuti inogona kuuraya uropi huputi. Kwaiva nevakafa zvitatu mumakore ose ekunyorwa kwekutongwa kwete nekuda kwekuwedzera kwezvirwere, izvo zviitiko zviviri, zvakanzi zvakabatana ne axicabtagene ciloleucel. Zvakare, kliniki yekugadzirwa kwemishonga iyi inotarisirwa kuenderera nekuchenjerera.
GoCAR-T, Mutevedzeri weMishonga Yakasimba neBellicum Pharmaceuticals
Houston, Texas-yakagadzirwa neBellicum Pharmaceuticals, Inc., ine vashandisi vezvinodhaka zvinosanganisira BPX-601 (gombe reGoCAR-T, nokuda kwezvipembenene zvakasimba, zvakagadzirirwa neMMC inoshandiswa kushandura kushandiswa kunatsiridza kushanda, chikamu I), uye BPX-701 (yakakwirira -affinity TCR candidate, nokuda kwezviremera zvakasimba , zvakagadzirwa neCaspaCIDe kuchengetedzwa kwekuchengetedza, chikamu I).
Saka, izvi zvinorevei? Chaizvoizvo, boka iri riri kushanda pakuchenesa CAR T-cell teknolojia kuitira kuti rizoita kuti chiremba anzwe kutonga pamusoro pemhinduro ye-T-cell. GoCAR-T masero akagadzirirwa kungogadziridzwa zvizere kana akaiswa kune ose masero emukenza uye anoshanda anonzi rimiducid. Saka, chinangwa, chiremba aizokwanisa kudzora kuwedzerwa kwemagetsi eC CAR-T kuburikidza nekugadzirisa purogiramu yehumiducid administration, asi kuurawa kwei cell kuchiri kuitika nenzira inoratidzika.
Vamwe Vanyori
Juno ikambani iri kutarisa JCAR017, CAR-T chigadzirwa chinoshandiswa neCD19. Juno ari kutarisira kuwana JCAR017 pamusika kutanga muna 2018 yeNHL. Iyo kambani yakabatana naCengene mune izvi.
ZIOPHARM Oncology ine CD19-yakagadzirwa uye iri kushanda kune CD33-yakananga CAR T-cell therapy yekudzorerwa / kukanganisa zvakanyanya myeloid leukemia (AML). NantKwest ndiyo inonzi immunotherapy inoshandiswa pakushandisa muurayi wenyama (NK) masero ekurapa kenza, zvirwere zvinotapukira, uye zvirwere zvinopisa.
Nhengo ye NK cell-based platform yakagadzirirwa kuita kuti sero rekurwisana nekenza kana masero ane utachiona nemitatu yakasiyana-siyana-kuuraya zvakashandiswa uchishandisa NK cells (aNK); kuponda-kupesana-kupfurikidza kupfurikidza nekushandiswa kweHNKs, uye kurwiswa kunourayiwa kushandiswa uchishandisa taNKs.
Shoko Rinobva
Mamwe emigumisiro yepakutanga kubva kuC CAR-T yechirongwa chechirwere yakave ichifadza zvikuru, kupa mishonga mitsva kumapoka evarwere vasina kumboita zvisarudzo zvakadaro zvisati zvaitika. Ikoko kwavewo nekukundikana, zvisinei, uye kunyanya kunetseka kwekutambudza kuita kuti kurapa uku kuve kwakabudirira sezvinobvira nehuwandu hwehuwandu hwehudha.
Sezvo vatsvakurudzi vanodzidza zvakawanda pamusoro pemararamiro ezvirwere zvekuzvidzivirira mumuviri anobatanidzwa mune remishonga iyi, uye zvinokonzerwa nemarangariro akafanirwa, mifananidzo yakajeka yezvipingamupinyi uye zvikomborero zvinofanira kubuda.
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> Bhoj VG, Arhontoulis D, Wertheim G, et al. Kushivirira kwemazuva akawanda akachengetedza masero eplasma uye kudzivirira kwemashuga mune vanhu vanoita CD19-inotungamirirwa CAR T-cell therapy. Ropa. 2016; 128 (3): 360-370.
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