Kev Tsim Kho Antibody yog dab tsi?

Nrog kev pab los ntawm kev tsim cov tshuaj tiv thaiv kab mob, nws tau ua tau los hloov kho qhov loj me ntawm cov tshuaj, pharmacokinetics, immunogenicity, binding affinity, specificity thiab effector function ntawm cov tshuaj tiv thaiv kab mob. Tom qab synthesizing cov tshuaj tiv thaiv kab mob, qhov kev khi tshwj xeeb ntawm cov tshuaj tiv thaiv kab mob ua rau lawv muaj txiaj ntsig zoo hauv kev kuaj mob thiab kev kho mob. Los ntawm kev tsim cov tshuaj tiv thaiv kab mob, lawv tuaj yeem ua tau raws li qhov xav tau ntawm kev kho mob thiab kev loj hlob thaum ntxov.

Lub hom phiaj ntawm kev tsim cov tshuaj tiv thaiv kab mob yog los tsim thiab tsim cov haujlwm tshwj xeeb, ruaj khov uas cov tshuaj tiv thaiv ntuj tsim tsis tuaj yeem ua tiav, tso lub hauv paus rau kev tsim cov tshuaj tiv thaiv kev kho mob.

Alpha Lifetech, nrog nws cov kev paub dhau los hauv kev tsim cov tshuaj tiv thaiv kab mob, tuaj yeem muab cov kev pabcuam monoclonal thiab polyclonal antibody rau ntau hom tsiaj, nrog rau kev tsim cov tsev qiv ntawv antibody phage thiab kev tshuaj ntsuam. Alpha Lifetech tuaj yeem muab cov neeg siv khoom nrog cov tshuaj tiv thaiv biosimilar zoo thiab cov khoom lag luam recombinant protein, nrog rau cov kev pabcuam sib xws, los tsim cov tshuaj tiv thaiv zoo, tshwj xeeb heev, thiab ruaj khov. Los ntawm kev siv cov tshuaj tiv thaiv kab mob, cov platform protein thiab cov kab ke phage, peb muab cov kev pabcuam uas npog cov khoom tsim cov tshuaj tiv thaiv kab mob sab saud thiab sab hauv qab, suav nrog cov kev pabcuam kev siv tshuab xws li kev ua kom cov tshuaj tiv thaiv kab mob tib neeg, kev ntxuav cov tshuaj tiv thaiv kab mob, kev txheeb xyuas cov tshuaj tiv thaiv kab mob, thiab kev lees paub cov tshuaj tiv thaiv kab mob.

Theem pib ntawm kev tsim tshuaj tiv thaiv kab mob muaj feem cuam tshuam nrog ob txoj kev siv tshuab:

--Kev siv tshuab DNA sib txuas ua ke

--Kev siv tshuab Hybridoma

Kev loj hlob sai ntawm kev tsim tshuaj tiv thaiv kab mob muaj feem cuam tshuam nrog peb txoj kev siv tshuab tseem ceeb:

--Kev siv tshuab cloning noob caj noob ces thiab polymerase chain reaction

--Kev qhia tawm cov protein: Cov protein sib xyaw ua ke yog tsim los ntawm cov txheej txheem qhia tawm xws li cov poov xab, cov kab mob zoo li tus pas nrig, thiab cov nroj tsuag

--Kev tsim qauv siv computer los pab

Cov tshuaj tiv thaiv kab mob thawj zaug tau ua rau tib neeg tsim cov tshuaj tiv thaiv chimeric, qhov twg thaj tsam hloov pauv ntawm cov tshuaj tiv thaiv monoclonal nas tau txuas nrog thaj tsam tas mus li ntawm cov tshuaj IgG tib neeg. Thaj tsam khi antigen (CDR) ntawm cov tshuaj monoclonal nas tiam thib ob tau hloov mus rau hauv tib neeg IgG. Tsuas yog thaj tsam CDR xwb, txhua yam tshuaj tiv thaiv kab mob lwm yam yuav luag yog cov tshuaj tiv thaiv tib neeg, thiab kev siv zog tau ua kom tsis txhob ua rau tib neeg tiv thaiv nas antibody (HAMA) teb thaum siv cov tshuaj clone nas rau kev kho tib neeg.

 

Yuav kom tsim tau lub tsev qiv ntawv phage display, thawj kauj ruam yog kom tau txais cov noob caj noob ces encoding antibodies, uas tuaj yeem cais tawm ntawm B cell ntawm cov tsiaj uas tau txhaj tshuaj tiv thaiv kab mob (kev tsim kho tsev qiv ntawv tiv thaiv kab mob), rho tawm ncaj qha los ntawm cov tsiaj uas tsis tau txhaj tshuaj tiv thaiv kab mob (kev tsim kho tsev qiv ntawv ntuj), lossis txawm tias sib sau ua ke hauv vitro nrog cov khoom tawg ntawm cov noob caj noob ces antibody (kev tsim kho tsev qiv ntawv synthetic). Tom qab ntawd, cov noob caj noob ces raug nthuav dav los ntawm PCR, ntxig rau hauv plasmids, thiab qhia tawm hauv cov kab ke tsim nyog (kev qhia tawm poov xab (feem ntau yog Pichia pastoris), kev qhia tawm prokaryotic (feem ntau yog E. coli), kev qhia tawm ntawm cov tsiaj txhu, kev qhia tawm ntawm cov nroj tsuag, thiab kev qhia tawm ntawm cov kab mob uas muaj cov kab mob zoo li tus pas nrig). Qhov feem ntau yog lub kaw lus qhia tawm ntawm E. coli, uas koom ua ke cov kab ke encoding antibody tshwj xeeb rau ntawm phage thiab encodes ib qho ntawm cov protein phage plhaub (pIII lossis pVIII). Kev sib xyaw ua ke ntawm cov noob caj noob ces, Thiab tso tawm rau ntawm qhov chaw ntawm bacteriophages. Lub hauv paus ntawm cov thev naus laus zis no yog los tsim lub tsev qiv ntawv phage display, uas muaj qhov zoo dua li cov tsev qiv ntawv ntuj uas nws tuaj yeem muaj kev khi tshwj xeeb. Tom qab ntawd, cov tshuaj tiv thaiv kab mob uas muaj qhov tshwj xeeb ntawm cov antigen raug tshuaj xyuas los ntawm cov txheej txheem xaiv kab mob, cov antigens uas xav tau raug kho, cov phages uas tsis khi raug ntxuav ntau zaus, thiab cov phages uas khi raug ntxuav kom huv si ntxiv. Tom qab peb lossis ntau qhov kev rov ua dua, cov tshuaj tiv thaiv kab mob siab thiab cov tshuaj tiv thaiv kab mob siab raug rho tawm.

Daim Duab 3: Kev Tsim Kho thiab Kev Tshuaj Xyuas Lub Tsev Qiv Ntawv Antibody

Cov thev naus laus zis DNA recombinant siv tau los tsim cov khoom tiv thaiv kab mob. Fab antibodies tsuas yog tuaj yeem hydrolyzed los ntawm gastric protease los tsim (Fab ') 2 fragments, uas tom qab ntawd zom los ntawm papain los tsim cov khoom Fab ib leeg. Cov khoom Fv muaj VH thiab VL, uas muaj kev ruaj khov tsis zoo vim tsis muaj disulfide bonds. Yog li ntawd, VH thiab VL txuas ua ke los ntawm peptide luv luv ntawm 15-20 amino acids los tsim ib qho saw hlau hloov pauv fragment (scFv) antibody nrog qhov hnyav molecular ntawm kwv yees li 25KDa.

Kev kawm txog cov qauv tshuaj tiv thaiv kab mob hauv Camelidae (Camel, LIama, thiab Alpaca) tau piav qhia tias cov tshuaj tiv thaiv kab mob tsuas muaj cov saw hlau hnyav thiab tsis muaj cov saw hlau sib dua, yog li ntawd lawv thiaj li hu ua cov tshuaj tiv thaiv kab mob hnyav (hcAb). Cov kab mob hnyav uas hloov pauv tau hu ua cov tshuaj tiv thaiv kab mob ib leeg lossis nanobodies lossis VHH, nrog qhov loj ntawm 12-15 kDa. Raws li monomers, lawv tsis muaj disulfide bonds thiab ruaj khov heev, nrog rau kev sib raug zoo heev rau cov antigens.

Daim Duab 5: Cov Tshuaj Antibody Hnyav thiab VHH/ Nanobody

Kev qhia tawm dawb ntawm lub hlwb siv kev qhia tawm ntawm cov DNA ntuj lossis cov khoom siv los ua kom tiav cov protein synthesis hauv vitro, feem ntau siv E. coli expression system. Nws tsim cov protein sai sai thiab zam kev cuam tshuam metabolic thiab cytotoxic rau cov hlwb thaum tsim cov protein recombinant ntau hauv vivo. Nws kuj tseem tuaj yeem tsim cov protein uas nyuaj rau synthesize, xws li cov uas nyuaj rau hloov kho tom qab txhais lus lossis synthesize cov protein membrane.