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Ikpo Okwu Mmepe Ọgwụ Mgbochi Bispecific

Alpha Lifetech nwere ike inye ndị ahịa ihe nchọpụta dị mma nke na-eme ka ha nwee ike igbochi ọrịa na ngwaahịa na ọrụ protein ndị e ji eme ihe.

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Ikpo Okwu Mmepe Ọgwụ Mgbochi Bispecific

Alpha Lifetech nwere ike inye ndị ahịa ihe nchọpụta antibody dị mma yana ngwaahịa na ọrụ protein recombinant. Anyị nwere ike ịkwadebe antibody nwere arụmọrụ dị elu, nkọwapụta siri ike, na ezigbo nkwụsi ike. Alpha Lifetech nwere ọtụtụ ngwa na akụrụngwa nhicha antibody, nke nwere ike inye ọrụ nhicha antibody site na isi mmalite dị iche iche dịka oke bekee, atụrụ, ọkụkọ, na òké monoclonal antibody, yana ọrụ nhicha Protein A/G affinity purification na ọrụ nkewa na nhicha antibody. Dabere na usoro ikpo okwu zuru oke nke ikpo okwu nchọpụta antibody, ikpo okwu protein, wdg., anyị na-ekpuchi ọrụ elu na ala nke mmepụta antibody, ma nwee ike inye ọrụ teknụzụ site na nkwadebe antibody, nhicha antibody bispecific na nkewa na nhicha antibody, usoro antibody, nkwenye antibody, wdg,, nke enwere ike iji maka ọgwụgwọ antibody bispecific.

Ọgwụ mgbochi monoclonal na-ezo aka na immunoglobulins nke otu mkpụrụ ndụ B mepụtara nke nwere nnukwu nkọwapụta maka antigens ma ọ bụ epitopes. Emebere mmepụta ọgwụ mgbochi monoclonal na mbụ site na iji teknụzụ hybridoma mepụta ọgwụ mgbochi òké. Karịsịa, site na ijikọ mkpụrụ ndụ spleen site na òké a gbanyere ọgwụ mgbochi yana mkpụrụ ndụ myeloma site na mmadụ ma ọ bụ òké, a na-emepụta mkpụrụ ndụ hybridoma, nke na-ewepụta ọgwụ mgbochi ụfọdụ. A na-ejikarị ọgwụ mgbochi monoclonal òké emepụta na nyocha anụmanụ na nchọpụta ọrịa mgbe ọrụ nhicha gasịrị. Agbanyeghị, ahụ mmadụ ga-emepụta nzaghachi mgbochi na protein òké mba ọzọ, yabụ enwere oke mgbochi dị ukwuu na ojiji ahụike nke mmepụta ọgwụ mgbochi monoclonal òké. Mgbe e mesịrị, ndị mmadụ jiri "humanization" kwadebe ọgwụ mgbochi monoclonal site na òké, ma jiri teknụzụ injinịa mkpụrụ ndụ ihe nketa gbanwee ọgwụ mgbochi òké ka ọ nwee mpaghara immunoglobulin mmadụ na-adịgide adịgide iji belata ike immunogenicity ha. A makwaara ụdị ọgwụ mgbochi a dị ka ọgwụ mgbochi monoclonal nke a gbanyere mmadụ. Na mgbakwunye, iji mkpụrụ ndụ mmadụ mepụta ọgwụ mgbochi monoclonal a na-akpọ nkwadebe antibody monoclonal mmadụ dum. A na-ejikarị ọgwụ mgbochi Monoclonal eme ihe n'ọtụtụ ebe na ngwa biomedical na ọgwụgwọ. N'ime nnyocha ahụike, enwere ike iji ọgwụ mgbochi monoclonal mee ihe dị ka ọgwụ mgbochi immunomodulators, enwere ike iji ọgwụ mgbochi monoclonal agwọ ọrịa maka chemotherapy kansa na ọgwụgwọ ọrịa nje, a na-ejikwa mmepe nke monoclonal antibody conjugates eme ihe maka ọgwụgwọ kansa.

Okwu Mmalite nke Antibody Bispecific

Na 1960, e wepụtara echiche nke ọgwụ mgbochi bispecific. Ọgwụ mgbochi bispecific, nke a makwaara dị ka ọgwụ mgbochi monoclonal bispecific, bụ ọgwụ mgbochi e ji aka mepụta site na iji teknụzụ injinịa mkpụrụ ndụ ihe nketa. Dịka ọgwụ mgbochi artificial engineering, ọgwụ mgbochi bispecific na-abụkarị nke obere klas IgG ma nwee akụkụ njikọ antigen na-elekwasị anya na subunit CD3. Ọgwụ mgbochi bispecific nwere ebe njikọ antigen abụọ akọwapụtara nke nwere ike ijikọ ma mata antigen abụọ dị iche iche n'otu oge, ma ọ bụ epitopes abụọ dị iche iche nke antigen. Ma e jiri ya tụnyere ọgwụ mgbochi monoclonal, ọgwụ mgbochi bispecific nwere ebe njikọ antigen ọzọ akọwapụtara, si otú a nwee nkọwapụta siri ike na ikike ebumnuche, nke nwere ike ilekwasị anya na mkpụrụ ndụ tumor nke ọma ma belata nsí ebumnuche. Ọgwụ mgbochi bispecific nwere ike ịrụ ọrụ dị iche iche n'otu oge, dị ka ịchọta mkpụrụ ndụ na-alụso ọrịa ọgụ, igbochi ụzọ mgbaàmà, na igbu mkpụrụ ndụ tumor ozugbo. A na-akwadebe ọgwụ mgbochi bispecific mbụ site na njikọta kemịkalụ ma ọ bụ njikọ mkpụrụ ndụ, mana usoro a nwere ike ịga n'ihu nwayọ n'ihi njikọta na-enweghị usoro na ihe isi ike n'ịwapụ njikọta ebumnuche. Site na mmepe na-aga n'ihu nke teknụzụ injinịa mkpụrụ ndụ ihe nketa, e mepụtala ọtụtụ ikpo okwu teknụzụ ọhụrụ, dị ka knots in holes (KIH), CrossMab, DVD Ig, wdg. Ikpo okwu ndị a na-edozi nsogbu dị ka agbụ ígwè dị arọ na enweghị njikọ nke agbụ ígwè dị mfe, ma na-eme ka otu na mmepụta nke ọgwụ mgbochi bispecific dịkwuo mma.
bsAbs
Fig. 1. Nchịkọta atụmatụ dị mfe nke usoro atụmatụ maka ọgwụ mgbochi bispecific (bsAbs) na nnwale ahụike maka oncology.(Isi mmalite nke eserese a: Nyocha nke ọgwụ mgbochi bispecific na ihe owuwu antibody na oncology na ihe ịma aka ahụike - ScienceDirect)

Teknụzụ Mmepụta Ọgwụ Mgbochi Bispecific

Ụzọ ndị bụ isi maka mmepụta ọgwụ mgbochi bispecific gụnyere njikọ kemịkalụ, hybridoma isi anọ, na nkwadebe antibody engineering genetic engineering. N'ime ha, usoro njikọ kemịkalụ na-ejikọ iberibe antibody IgG abụọ ma ọ bụ F (ab ') abụọ na-enweghị nsogbu n'ime ọgwụ mgbochi bispecific site na iji ihe njikọta kemịkalụ dị ka phthalimide na dithioacylbenzoic acid. Usoro a dị mfe ma dị mfe ịrụ ọrụ, mana ọ nwere ike imebi ebe njikọ antigen, belata ọrụ antibody, ihe njikọ ahụ n'onwe ya nwekwara oke nke kansa. Usoro hybridoma isi anọ dabere na njikọta nke mkpụrụ ndụ somatic site na ahịrị mkpụrụ ndụ hybridoma abụọ dị iche iche iji gosipụta òké IgG kwekọrọ. Site na teknụzụ injinia mkpụrụ ndụ ihe nketa, enwere ike ịgbanwe antibody mkpụrụ ndụ ihe nketa ka ọ mepụta antibody bispecific. E wuru antibody monoclonal abụọ dị iche iche, e kewarakwa iberibe Fab ma ọ bụ nnukwu yinye na mpaghara mgbanwe nke yinye ọkụ nke ọgwụ mgbochi abụọ ahụ iche. Site na mmeghachi omume njikọ ma ọ bụ teknụzụ njikọta yinye, ejikọtara iberibe abụọ ahụ iji mepụta antibody bispecific. Ọ bụ ezie na mgbagwoju anya nke teknụzụ injinia mkpụrụ ndụ ihe nketa dị elu, ọ bụ ugbu a usoro a na-ejikarị eme ihe maka mmepụta antibody bispecific iji gbanwee nhazi na ọrụ nke antibody. Mgbe a na-eme nhazi ọgwụ mgbochi bispecific, a pụrụ iji ụkpụrụ nke mmeghachi omume antibody cross reactivity mee ihe, mana mmeghachi omume antibody cross reactivity nwere ike ibute mmeghachi omume na-abụghị nke akọwapụtara, yabụ a ga-atụle ya nke ọma n'ọrụ bara uru nke imepụta ọgwụ mgbochi bispecific, dịka ọgwụgwọ antibody bispecific.

Nhicha nke ihe mgbochi bispecific

Nhicha ihe mgbochi nje nke bispecific bụ usoro nke ikewapụ na ime ka ihe mgbochi nje dị ọcha nke ukwuu dị ọcha. A na-eji ụzọ abụọ, centrifugation na nzacha miri emi, ewepụ ụfọdụ ihe na-agbaze agbaze. A na-ejide ihe mgbochi nje nke bispecific na mbụ site na iji affinity chromatography. Maka ihe mgbochi nje nke bispecific dị ka IgG, a na-eji protein A affinity chromatography, ebe maka ihe mgbochi nje nke na-abụghị IgG dị ka bispecific, enwere ike iji chromatography affinity based light yinye. Mgbe nke ahụ gasịrị, a na-etinye ihe mgbochi nje ahụ n'okpuru ọnọdụ pH dị ala maka oge ụfọdụ, na-eme ka nhazi protein dị n'elu envelopu nje ahụ ghara ịdị irè, si otú a na-efunahụ ikike ibute mkpụrụ ndụ. A na-eme nzacha miri emi dị n'etiti iji wepụ ihe ndị na-adịghị ọcha dị ka protein sel host (HCP). A na-eme ka ịdị ọcha nke ihe mgbochi nje dịkwuo mma site na usoro dị ka ion exchange chromatography, a na-ewepụkwa nje ọ bụla fọdụrụ site na usoro nanofiltration ma ọ bụ ultrafiltration. N'ikpeazụ, a na-etinye ihe nlele ahụ ma jiri ihe nchekwa nhazi kwesịrị ekwesị dochie ya.

Ọrụ Mmepụta Ọgwụ Mgbochi Bispecific

Nzọụkwụ Ọdịnaya Ọrụ Usoro iheomume
Njikọta Mkpụrụ Ndụ Ihe
Mmepụta nke usoro nhazi atọ dị iche iche, mmepụta ọhụrụ nke plasmids DNA antibody recombinant
Izu abụọ ruo atọ
Nnwale obere nha Mmepụta nke protein antibody bispecific → Obere ngosipụta na ahịrị mkpụrụ ndụ anụmanụ → Nkwenye site na SDS-PAGE → Nyocha njikọ na antigens protein recombinant site na ELISA → Ntụnyere nke klọn na antibody nne Izu 5-6
Chọpụta
Ngosipụta nke ọgwụ mgbochi abụọ mbụ zuru oke nke nwere ogologo abụọ → Nyocha njikọ site na ELISA → Nyocha ELISA nke ọgwụ mgbochi ndị nwere mgbochi òké a matara
Izu otu
Mmepụta Ọgwụ Mgbochi
Mmepụta ọgwụ mgbochi buru ibu
Izu 3-4

Uru Anyị

Anyị na-ekpuchi ọrụ mmepụta ọgwụ mgbochi ọrịa site na elu na ala, anyị nwekwara ike inye ọrụ teknụzụ site na nkwadebe ọgwụ mgbochi ọrịa, nhicha ọgwụ mgbochi ọrịa bispecific na nkewa na nhicha ọgwụ mgbochi ọrịa, usoro ọgwụ mgbochi ọrịa, nkwenye ọgwụ mgbochi ọrịa, wdg, nke enwere ike iji maka ọgwụgwọ ọgwụ mgbochi bispecific.

  • dst-11

    Ngosipụta Dị Elu

    Nnukwu protein na mkpụrụ ndụ CHO.

  • dst-12

    Nchekwa Dị Ike

    - n'ime ọbara - ihe karịrị izu abụọ na okpomọkụ 37 Celsius.

  • dst-13

    Enweghị Nsogbu Ngwọta

    >30 mg/ml

  • dst-14

    Mkpụrụ ndụ kwụsiri ike

    E mepụtala ọtụtụ ahịrị mkpụrụ ndụ kwụsiri ike nwere antigens etuto ahụ iji kwado ọtụtụ ọgwụ mgbochi bispecific.

Ọrụ Ndị Metụtara Ya

Ọ bụrụ na ị nwere ajụjụ ọ bụla, biko nweere onwe gị ịkpọtụrụ anyị n'oge ọ bụla.

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