Daim Ntawv Qhia Txog ADC Cov Txheej Txheem Kev Npaj Tshuaj Txhaum Cai

Raws li cov ntaub ntawv kuaj mob qog noj ntshav thoob ntiaj teb tshiab tshaj plaws rau xyoo 2020 tau tshaj tawm los ntawm Lub Chaw Haujlwm Saib Xyuas Kev Tshawb Fawb Txog Kev Tshawb Fawb Hauv Ntiaj Teb (IARC) ntawm World Health Organization (WHO), Tuam Tshoj tau dhau los ua "lub tebchaws mob qog noj ntshav".

 

Xyoo 2020, yuav muaj 19.29 lab tus neeg mob qog noj ntshav tshiab hauv ntiaj teb, ntawm 4.57 lab yuav yog cov neeg mob qog noj ntshav tshiab hauv Suav teb, nrog 2.48 lab tus txiv neej thiab 2.09 lab tus poj niam, suav txog 23.7% ntawm lub nra hnyav thoob ntiaj teb, thiab tus lej ntawm Cov mob qog noj ntshav tshiab tshaj li cov neeg mob qog noj ntshav tshiab nyob hauv lub ntiaj teb. 9.96 lab thoob ntiaj teb kev tuag mob qog noj ntshav tau tshaj tawm xyoo 2020, ntawm 3.

 

Thoob plaws ntiaj teb, lub luag haujlwm mob qog noj ntshav tau kwv yees tias yuav nce 50% hauv 2040 piv rau 2020, lub sijhawm no tus naj npawb ntawm cov mob qog noj ntshav tshiab yuav ncav cuag ze li 30 lab, vim muaj cov neeg laus zuj zus.

 

Raws li cov neeg mob coob coob thiab kev tuag, kev txhim kho cov tshuaj tiv thaiv kab mob zoo uas tuaj yeem txhim kho cov theem tam sim no ntawm kev kho mob qog noj ntshav thiab ua kom cov neeg mob muaj sia nyob ntev yog qhov xav tau sai thiab tam sim no tau dhau los ua ib lub hom phiaj tseem ceeb ntawm cov neeg tsim tshuaj tshiab thoob ntiaj teb. Tau ntau xyoo dhau los, cov kev kho mob tau txais kev saib xyuas ntau ntxiv los ntawm cov kws tshawb fawb txog lawv txoj kev tswj hwm kev noj qab haus huv thiab kev nyab xeeb. Cov tshuaj tiv thaiv ib txwm muaj nyob hauv lub cev tiv thaiv kab mob, thiab cov tshuaj tiv thaiv kab mob tau dhau los ua ib qho ntawm cov kev tshawb fawb hotspots. Kev txiav txim los ntawm cov npe muag tshuaj thoob ntiaj teb nyob rau xyoo tas los no, cov tshuaj tiv thaiv kab mob sib txuas tau tsim kho sai heev, qhia txog kev lag luam zoo.

 

Antibody-coupled tshuaj (ADC) yog ib hom tshiab ntawm biopharmaceutical zoo heev uas txuas cov tshuaj tiv thaiv kab mob nrog cov tshuaj lom me me cytotoxic loads los ntawm kev sib txuas, uas yog ib qho ntawm cov chav kawm tshuaj sai sai hauv oncology nyob rau xyoo tas los no, thiab tam sim no nws tau dhau los ua ib qho tshuaj tiv thaiv kab mob. kub kev taw qhia nyob rau hauv kev tshawb fawb thiab kev loj hlob ntawm cov tshuaj antitumor, qhib ib tug tshiab tshooj nyob rau hauv kev kho mob ntawm cov qog.

 

Ntawm lawv, cov tshuaj tiv thaiv tuaj yeem paub cov qog antigens uas muaj qhov tshwj xeeb, thiab tom qab txhaj tshuaj, cov tshuaj tau muab faib rau cov ntaub so ntswg los ntawm cov ntshav ncig thiab khi rau cov qog nto antigens.Cov complexes ntawm ADCs thiab antigens undergo endocytosis, internalizing lub me me molecule cytotoxic load lawv. nqa mus rau hauv cov qog hlwb, raug thauj mus rau lysosomes kom tso tawm nyob rau hauv ib tug heev npaum thiab active daim ntawv, uas induces apoptosis ntawm cancer hlwb los ntawm DNA puas los yog inhibition ntawm microtubule synthesis. Vim muaj qhov zoo dua ntawm ob lub hom phiaj ntawm cov tshuaj monoclonal antibody thiab kev ua haujlwm siab ntawm cytotoxicity hauv cov ntaub so ntswg, ADC cov tshuaj tuaj yeem tua tau thiab ua rau mob qog hlwb, nrog rau cov teebmeem qis dua li cov tshuaj kws khomob, thiab ua tau zoo dua li cov tshuaj tiv thaiv kab mob qog noj ntshav, uas yog lub hotspot ntawm qog lub tshiab tshuaj tshawb fawb thiab kev loj hlob nyob rau hauv xyoo tas los no.

 

Kev tsim cov txheej txheem ntawm ADC tshuaj

 

ADC cov txheej txheem tsim khoom thiab kev npaj yog qhov nyuaj, raws li cov txheej txheem sib txuas sib txawv thiab cov txheej txheem, tag nrho cov txheej txheem tuaj yeem muab faib ua peb kauj ruam: monoclonal antibody ntau lawm, cytotoxic tshuaj / linker ntau lawm, thiab ADC cov tshuaj npaj thiab npaj ntau lawm.

 

Monoclonal antibody ntau lawm: Antibody molecules yog cov khoom tseem ceeb ntawm ADC cov tshuaj, thiab lawv cov haujlwm tseem ceeb rau kev ua tau zoo ntawm cov tshuaj. Hauv cov txheej txheem tsim khoom, cov tshuaj tiv thaiv kab mob ua ntej yuav tsum tau qhib. Cov txheej txheem tshuaj, xws li kev siv cov activators (xws li, sulfonates) los yog recombinant antibody engineering cov tswv yim, feem ntau yog ua haujlwm rau ob peb pab pawg tshwj xeeb ntawm cov tshuaj tiv thaiv molecule nrog cov txuas lossis co toxins. Cov activated antibody molecule muaj ntau dua reactivity thiab tuaj yeem khi tshwj xeeb rau lub hom phiaj antigen.

 

Cytotoxic Drugs/Linker Production: Kev sib txuas ntawm cov tshuaj tua kab mob rau cov tshuaj tiv thaiv kab mob yog ib qho ntawm cov kauj ruam tseem ceeb hauv kev npaj cov tshuaj ADC. Ib qho txuas yog ib qho tshuaj uas txuas cov tshuaj tiv thaiv kab mob rau cov tshuaj lom molecule, feem ntau yog ib qho kev sib txuas nrog kev sib raug zoo, kev ruaj ntseg siab thiab tsis muaj tshuaj lom. Cov tshuaj lom molecule yog siv los tua lub hom phiaj ntawm tes los yog inhibit nws txoj kev loj hlob. Los ntawm lub luag haujlwm ntawm kev sib txuas ntawm tus txuas, cov tshuaj tiv thaiv kab mob thiab cov tshuaj lom molecules tau ua ke los tsim cov khoom xyaw nquag ntawm ADC tshuaj. Cov txheej txheem kev sib txuas thiab cov txheej txheem sib txuas, uas txiav txim siab cov yam ntxwv zoo xws li tus nqi ntawm cov tshuaj thauj khoom thiab hom kev thauj khoom thauj tshuaj, muaj feem cuam tshuam ncaj qha rau kev ua tau zoo thiab kev nyab xeeb ntawm ADC cov tshuaj. Ib qho zoo tagnrho ADC coupling lub tswv yim lossis thev naus laus zis yuav tsum muaj cov yam ntxwv hauv qab no: A. Cov khoom siv tshuaj lom neeg lossis cov pab pawg hauv kev sib txuas ntawm cov tshuaj tiv thaiv kab mob thiab cov molecule me me yuav tsum muaj kev ruaj khov txaus kom ntseeg tau tias lawv ruaj khov hauv cov hlab ntsha; B. Qhov chaw sib txuas yuav tsis cuam tshuam nrog kev ua haujlwm ntawm cov tshuaj tiv thaiv kab mob, tshwj xeeb, qhov tshwj xeeb thiab siab affinity ntawm kev khi rau lub hom phiaj antigen; C. Cov tshuaj tiv thaiv kev koom tes hauv cov txheej txheem sib txuas yuav tsum muaj kev xaiv txaus thiab rov ua haujlwm, thiab tib lub sijhawm, nws yuav tsum yooj yim los tswj cov tshuaj thauj khoom thiab thauj cov tshuaj.

 

Tam sim no ADC txuas thev naus laus zis tuaj yeem faib ua ob pawg. Ib qho yog kev sib txuas thev naus laus zis (non-site-specific coupling) kho los ntawm kev siv cov amino acid residues ib txwm muaj nyob rau hauv cov tshuaj tiv thaiv kab mob (xws li, sab-chain amino pawg ntawm nto lysine thiab pab pawg sparing ntawm inter-chain disulfide daim ntawv cog lus. txo), uas tau txais los ntawm 13 hom tshuaj ADC uas tam sim no nyob rau hauv khw; Lwm hom kev sib txuas thev naus laus zis yog los qhia cov pab pawg reactive rau hauv qhov chaw tshwj xeeb ntawm cov tshuaj tiv thaiv kab mob los ntawm kev hloov kho tshuaj, genetic engineering technology lossis enzyme hloov kho, thiab tom qab ntawd ua ke nrog cov tshuaj lom me me kom paub qhov chaw tshwj xeeb coupling technology (targeted coupling) . Cov tswv yim xws li kev tsim cov cysteine ​​site insertion, non-natural amino acid site insertion, enzyme-mediated thiab N-glycosylation-mediated coupling thiab lwm yam.

 

ADC Tshuag thiab npaj ntau lawm: Cov kauj ruam kawg hauv kev npaj cov tshuaj ADC yog ua kom tiav ADC Tshuag thiab npaj ntau lawm. Cov kauj ruam ua kom huv tshem tawm cov tshuaj tiv thaiv tsis sib xws, txuas thiab cov tshuaj lom molecules, nrog rau cov khoom tsis huv thiab cov khoom lag luam tsim tawm thaum lub sijhawm cov txheej txheem tshuaj tiv thaiv. Cov txheej txheem purification feem ntau yog siv ntau yam txheej txheem chromatographic (xws li, gel chromatography, ion exchange chromatography, thiab lwm yam) thiab cov tswv yim pom (xws li ultrafiltration, nanofiltration, thiab lwm yam). Tom qab ua kom huv huv, cov tshuaj ADC uas yuav tsum tau muaj yog qhov muaj purity siab thiab tsis muaj impurities, thiab tuaj yeem ua tau raws li qhov xav tau ntawm kev kho mob.

 

Raws li tuaj yeem pom los ntawm daim ntawv qhia txog kev tsim tshuaj ADC thiab kev npaj, txawm hais tias nws yog kev npaj ntawm monoclonal antibody, kev sib txuas ntawm cov khoom thauj, lossis kev tsim cov ADC cov kev daws teeb meem thiab kev npaj, lawv txhua tus yuav tsum ua kom tiav los ntawm cov tshuab lim membrane ( kev qhia meej ntawm fermentation broths, tsis hloov pauv, ultrafiltration penetration, thiab aseptic pom, thiab lwm yam).

 

Guidling Technology yog lub teb chaws high-tech enterprise tsom mus rau biopharmaceuticals, cell culture, purification thiab concentration ntawm biomedicine, kuaj mob thiab muaj kua. Peb tau ua tiav cov khoom siv lim dej centrifugal, ultrafiltration & microfiltration cassettes, cov kab mob lim, TFF system, qhov tob lim, hollow fiber, thiab lwm yam. Uas tau raws li daim ntawv thov scenarios ntawm biopharmaceuticals, kab lis kev cai ntawm tes, thiab lwm yam. Peb cov membranes thiab membrane lim tau dav siv nyob rau hauv concentration, extraction thiab sib cais ntawm pre-filtration, microfiltration, ultrafiltration thiab nanofiltration. Peb cov kab ntau cov khoom, los ntawm me me, ib leeg-siv chav kuaj pom mus rau ntau lawm filtration systems, sterility kuaj, fermentation, cell kab lis kev cai thiab lwm yam, ua tau raws li cov kev xav tau ntawm kev sim thiab ntau lawm. Guidling Technology tab tom tos ntsoov rau kev koom tes nrog koj!