Fa'avae mo le Atina'eina o Antibody Bispecific
E mafai e le Alpha Lifetech ona tuʻuina atu i tagata faʻatau oloa ma auaunaga e maua ai antibody ma recombinant protein. E mafai ona matou saunia antibodies e maualuga le aoga, malosi le faʻapitoa, ma lelei le mautu. O loʻo iai i le Alpha Lifetech le tele o meafaigaluega ma meafaigaluega e faʻamamāina ai antibody, e mafai ona tuʻuina atu auaunaga faʻamamāina antibody mai punaoa eseese e pei o le lapiti, mamoe, moa, ma isumu monoclonal antibodies, faʻapea foʻi ma auaunaga faʻamamāina o le Protein A/G affinity ma auaunaga vavaeʻese ma faʻamamāina antibody. E faʻavae i luga o le fausiaina atoatoa o le faiga o le faʻavae o le faʻavae o le antibody discovery platform, protein platform, ma isi, matou te aofia ai auaunaga i luga ma lalo o le gaosiga o antibody, ma e mafai ona tuʻuina atu auaunaga faʻapitoa mai le sauniuniga o antibody, bispecific antibody purification ma le vavaeʻese ma le faʻamamāina o antibody, antibody sequencing, antibody validation, ma isi, lea e mafai ona faʻaaogaina mo le bispecific antibody therapy.
O monoclonal antibodies e faasino i immunoglobulins e gaosia e se sela B e tasi e maualuga le fa'apitoa mo antigens po'o epitopes. O le gaosiga o monoclonal antibodies na muai saunia e fa'aaoga ai le tekinolosi hybridoma e gaosia ai antibodies isumu. Ae maise lava, e ala i le fa'apipi'iina o sela o le ate mai isumu ua puipuia ma sela myeloma mai tagata po'o isumu, e fausia ai sela hybridoma, lea e fa'asa'olotoina ai antibodies fa'apitoa. O monoclonal antibodies o isumu e fa'aaogaina tele i su'esu'ega a manu ma le su'esu'eina o fa'ama'i pe a uma auaunaga fa'amamāina. Peita'i, o le tino o le tagata o le a gaosia se tali puipuia i porotini isumu mai fafo, o lea e iai ni tapula'a taua i le fa'aogaina fa'aklinikal o le gaosiga o monoclonal antibodies o isumu. Mulimuli ane, na fa'aaoga e tagata le "humanization" e saunia ai monoclonal antibodies mai isumu, ma fa'aaoga le tekinolosi fa'ainisinia kenera e suia ai antibodies isumu ina ia iai se vaega tumau o le immunoglobulin tagata e fa'aitiitia ai lo latou immunogenicity. O lenei ituaiga antibody e ta'ua fo'i o le humanized monoclonal antibody. E le gata i lea, o le fa'aaogaina o sela o le tagata e gaosia ai monoclonal antibodies e ta'ua o le sauniuniga atoa o le monoclonal antibody a le tagata. O monoclonal antibodies e fa'aaogaina lautele i fa'aoga fa'afoma'i ma fa'aklinikal. I suʻesuʻega faafomaʻi, e mafai ona faʻaaogaina monoclonal antibodies o ni immunomodulators, e mafai ona faʻaaogaina monoclonal antibodies faʻafomaʻi mo chemotherapy o le kanesa ma togafitiga o faʻamaʻi pipisi viral, ma o le atinaʻeina o monoclonal antibody conjugates e faʻaaogaina tele mo togafitiga o le kanesa.
Faatomuaga i le Antibody Bispecific
I le 1960, na fautuaina ai le manatu o antibodies bispecific. O antibodies bispecific, e taʻua foʻi o antibodies monoclonal bispecific, o antibodies ia na faia faʻapitoa e faʻaaoga ai le tekinolosi faʻainisinia faʻasolopito. I le avea ai ma se antibody faʻapitoa faʻainisinia, o antibodies bispecific e masani ona i totonu o le IgG subclass ma o loʻo i ai se vaega e fusifusia ai antigen e faʻatatau i le subunit CD3. O antibodies bispecific e lua nofoaga faʻapitoa e fusifusia ai antigen e mafai ona fusifusia ma iloa ai antigens eseese e lua, poʻo ni epitopes eseese se lua o se antigen. Pe a faʻatusatusa i monoclonal antibodies, o antibodies bispecific e iai se isi nofoaga faʻapitoa e fusifusia ai antigen, ma o lea e sili atu le malosi o le faʻapitoa ma le gafatia e faʻatatau, lea e mafai ona sili atu le saʻo o le faʻatatauina o sela o le tumo ma faʻaitiitia ai le oona i fafo atu o le sini. E mafai e antibodies bispecific ona faia faʻatasi le tele o galuega faʻaletino, e pei o le faʻafaigaluegaina o sela puipuia, poloka auala faʻailoilo, ma fasiotia saʻo sela o le tumo. O antibodies bispecific muamua na saunia tele lava e ala i le faʻafefiloi vailaʻau poʻo le tuʻufaʻatasia o sela, ae o lenei metotia atonu na alualu i luma lemu ona o le tuʻufaʻatasiga faʻafuaseʻi ma le faigata i le vavaeʻeseina o le tuʻufaʻatasiga sini. Faatasi ai ma le atinaeina pea o tekinolosi inisinia kenera, ua tele fausaga faatekonolosi fou ua atiaeina, e pei o nonoa i pu (KIH), CrossMab, DVD Ig, ma isi. O nei fausaga e foia lelei ai faafitauli e pei o le le fetaui o filifili mamafa ma filifili mama, ma faaleleia atili ai le tutusa ma le fua o antibodies bispecific.

Ata 1 O se aotelega faigofie o faiga faatino ua fautuaina mo antibodies bispecific (bsAbs) i tofotofoga faafoma’i mo le oncology.(Punaoa o le ata: O se iloiloga o antibodies bispecific ma antibody constructs i oncology ma luʻitau faafomaʻi - ScienceDirect)
Tekonolosi o le Gaosiga o Antibodies Bispecific
O auala autū mo le gaosiga o antibody bispecific e aofia ai le fa'apipi'iina o vaila'au, hybridoma fa'avae e fa, ma le sauniuniga o antibody fa'ainisinia kenera. O nisi o ia mea, o le metotia fa'apipi'i vaila'au e fa'apipi'i ai ni IgG e lua e le'i a'afia pe ni fasi antibody F (ab ') 2 se lua i ni antibody bispecific e fa'aaoga ai vaila'au fa'apipi'i vaila'au e pei o le phthalimide ma le dithioacylbenzoic acid. O lenei metotia e faigofie ma faigofie ona fa'agaoioia, ae e ono fa'aleagaina ai le nofoaga e fusifusia ai antigen, fa'aitiitia ai le gaioiga o antibody, ma o le vaila'au fa'apipi'i lava ia e iai fo'i se tulaga o le carcinogenicity. O le metotia hybridoma fa'avae e fa e fa'avae i luga o le tu'ufa'atasia o sela somatic mai laina eseese e lua o sela hybridoma e fa'aalia ai le IgG o isumu e fetaui. E ala i le tekinolosi fa'ainisinia kenera, e mafai ona suia kenera antibody e fausia ai ni antibody bispecific. E lua ni antibody monoclonal eseese na fausia, ma o fasi Fab po'o vaega eseese o le filifili mamafa ma le filifili mama o antibody e lua na vaeluaina eseese. E ala i le cross-linking reaction po'o le tekinolosi toe fa'apipi'iina o filifili, na tu'ufa'atasia ai fasi e lua e fausia ai se antibody bispecific. E ui lava i le lavelave o le tekinolosi fa'ainisinia kenera e maualuga tele, o le auala sili lea ona fa'aaogaina i le taimi nei mo le gaosiga o antibody bispecific e fetu'una'i ai le fausaga ma le galuega a antibody. A faʻatinoina le mamanuina o le antibody bispecific, e mafai ona faʻaaogaina le mataupu faavae o le antibody cross reactivity, ae o le antibody cross reactivity e mafai ona mafua ai ni tali e le patino, o lea o le a mafaufau lelei i ai i le faʻaogaina moni o le mamanuina o le antibody bispecific, e pei o le togafitiga o le antibody bispecific.
Fa'amamāina o Antibodies Bispecific
O le fa'amamāina o le antibody bispecific o le faiga lea o le vavae'eseina ma le fa'amamāina o antibody fa'amoemoe e maualuga le mama. E lua auala, o le centrifugation ma le deep filtration, e fa'aaogaina e aveese ai nisi o mea leaga e mafai ona soluble. O le antibody bispecific fa'amoemoe e muamua pu'eina e ala i le affinity chromatography. Mo antibody bispecific e pei o le IgG, e fa'aaogaina le protein A affinity chromatography, ae mo antibody bispecific e le pei o le IgG, e mafai ona fa'aaogaina le light chain based affinity chromatography. Mulimuli ane, e fa'asusu le antibody i lalo o tulaga pH maualalo mo se vaitaimi patino, ma mafua ai ona fa'alavelaveina le fausaga o le porotini i luga o le ufiufi o le siama, ma leiloa ai le mafai ona a'afia ai sela. E faia le fa'amamāina loloto vaeluaga e aveese atili ai mea leaga e pei o porotini o sela talimalo (HCP). E fa'aleleia le mama o antibody e ala i auala e pei o le ion exchange chromatography, ma so'o se siama o totoe e aveese e ala i le nanofiltration po'o le ultrafiltration techniques. Mulimuli ane, e fa'apotopoto le fa'ata'ita'iga ma sui i se formulation buffer talafeagai.
Fa'asologa o Galuega mo le Gaosiga o Antibodies Bispecific
| Laasaga | Mataupu o Auaunaga | Taimi Fa'atulagaina |
|---|---|---|
| Fa'asologa o Kene | Fa'atupuina o ni mamanu eseese e o'o atu i le 3 o fa'asologa, fa'atupuina o ni plasmids DNA recombinant antibody de novo | 2-3 vaiaso |
| Su'ega Laiti | Gaosiga o porotini antibody bispecific → Fa'aaliga la'ititi i laina sela o mammalian → Fa'amaoniga e ala i le SDS-PAGE → Su'esu'ega fusifusia ma antigens porotini recombinant e ala i le ELISA → Fa'atusatusaga o clones ma antibodies matua | 5-6 vaiaso |
| Fa'ailoa | Fa'aalia o ulua'i antibodies bispecific atoa e lua → Su'esu'ega fusifusia e ala i le ELISA → Iloiloga a le ELISA o antibodies ua iloa e antibodies anti mouse | 1 vaiaso |
| Gaosiga o Antibody | Gaosiga tele o antibody | 3-4 vaiaso |
Afai e iai ni au fesili, fa'amolemole fa'afeso'ota'i matou i so'o se taimi.
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2018-07-16 

