Zotsatira za interleukin pakugwira ntchito kwa maselo a NK (IL-1β, IL-12, IL-15, IL-18, IL-21).

Gwero: T&L Biotechnology yotulutsidwa nthawi: 2023-08-24

 

Ma cell opha zachilengedwe amachokera ku mafupa a lymphoid Stem Cells ndipo ndi maselo obadwa nawo oteteza chitetezo m'thupi. Amatchedwa cytotoxicity yawo yomwe siinatchulidwe. Ntchito yakupha ya ma cell a NK sikuli malire ndi MHC ndipo sizidalira ma antibodies, chifukwa chake imatchedwa ntchito yakupha zachilengedwe. Imapha ma cell a chotupa kudzera pakuwonongeka kwachindunji ndi kutulutsa kwa ma cytokines, ndikupangitsa kuti ntchito yake yolimbana ndi khansa ikhale mutu wovuta kwambiri pakufufuza za khansa m'zaka zaposachedwa.

Interleukins ndi gulu la ma cytokines opangidwa ndi mitundu yosiyanasiyana ya maselo omwe amatha kuyendetsa kukula kwa maselo, kusiyanitsa, ndi chitetezo cha mthupi. Ambiri aiwo amagwirizana kwambiri ndi ma cell a NK, kapena amatenga nawo gawo mwachindunji pakuwongolera ma cell a NK, kapena amayang'anira mosadukiza ntchito ya ma cell a NK pokhudza ma cell ena achitetezo. Ma Interleukins monga IL-2, IL-15, ndi IL-18 amaonedwa kuti ndi zinthu zomwe zimalimbikitsa NK maselo ndipo zimagwiritsidwa ntchito kukulitsa ma cell a NK. Iwo ali ndi zabwino zoyang'anira zotsatira pa kutsegula ndi kusiyanitsa NK maselo. Kuwonjezera ma cytokines mu m`galasi chikhalidwe akhoza kwambiri kumapangitsanso kupha ntchito ya NK maselo.1, Kulimbikitsa NK selo kukula ndi kutsegula: IL-2/21

Kuyambira 1996, Soffer RJ et al. ndi rMafutaRTed kuti otsika mlingo mosalekeza kulowetsedwa ndi intermitted makonzedwe a IL-2 ndi kwambiri kukula zotsatira pa CD56 + NK maselo odwala metastatic khansa. Maselo ambiri a NK ali ndi zolandilira za IL-2 pamtunda wawo, ndipo IL-2 imapangitsa NK cytotoxicity pafupifupi maola 18-24. Kuphatikiza apo, IL-2 imathanso kuyambitsa kuchuluka kwa maselo a NK, omwe amayamba masiku 3-4 pambuyo pokondoweza. Njirayi ndi yakuti IL-2 ikhoza kuyambitsa kufotokoza kwa IL-2R mu maselo a NK α Chain, omwe angotchulidwa kumene α Unyolo ndi khungu loyambirira la selo β Chain ndi γ Kumangirira kwa unyolo kumapanga mapangidwe apamwamba ogwirizana, omwe amapangitsa kuti NK cell ichuluke pamaso pa IL-2.

gwero la zithunzi: Sharma R, et al. Mankhwala a Immunol 2018

 

Wendt K ndi al. adanenanso kuti poyang'anira NK cell function, IL-2 yokha imatha kulimbikitsa kukula kwa maselo a NK aumunthu, pamene kuphatikiza kwa IL-2 ndi IL-21 kumapanga mphamvu yowonjezera yowonjezera.

 

Li Q ndi al. adanenanso kuti IL-21 ili ndi mphamvu yowonjezera kwambiri pa maselo a NK aumunthu omwe amakula mu m'galasi, ndi kuwonjezeka kwa chiwerengero cha maselo. Zimalimbikitsanso kukula kwa maselo mu gawo la S la kayendedwe ka selo mkati mwa masabata awiri oyambirira a chikhalidwe. Zimalimbikitsanso maselo kuti alowe mu gawo la S la kayendedwe ka selo mkati mwa sabata yoyamba mpaka yachiwiri ya kulima.

gwero la chithunzi: Li Q, et al. Immunobiology. 2015.

 

2.Kupangitsa kusiyana kwa maselo a NK: IL-1β / 12/15
The chitetezo phenotype wa NK maselo ndi CD3-CD56 +, ndipo panopa ambiri amakhulupirira kuti amasiyanitsa mwachindunji m`mafupa hematopoietic tsinde maselo, ndiko, kuchokera CD34 + hematopoietic tsinde maselo. Zofufuza zambiri zatsimikizira kuti ma CD34 + omwe amachokera ku mafupa amatha kusiyanitsa mu NK maselo mu vitro kudzera mu induction ya cytokine, kupereka njira ina yochokera ku NK maselo.
Ambrosini et al. anasanthula zotsatira za IL-1β pa kusiyanitsa kwa maselo a NK kuchokera ku umbilical cord blood CD34 + precursor cells, ndipo deta inasonyeza kuti IL-1β imalepheretsa ILC3 pamene ikulimbikitsa kusasitsa kwa umbilical cord blood CD34 + precursor NK maselo.

Li Yan et al. adachita kuyesa kwa in vitro induction differentiation pa CD34 + leukemia cell yochokera ku mafupa a odwala omwe ali ndi acute myeloid leukemia. Maselo a CD34 + leukemia amatha kukopeka kuti asiyanitse kukhala ma cell a NK mu vitro omwe ali ndi ntchito ya cytotoxic. Kuphatikizika kwa IL-12 ndi 1L-15 ma cytokines kungapangitse kusiyana kwa maselo a NK, kupititsa patsogolo kupha kwa maselo a khansa ya m'magazi ndi majeremusi a TNF-α ndi IFN-γ.

Chithunzi chojambulidwa: Li Yan et al. Journal of Clinical Oncology, 2019

 

3.Kulimbikitsa NK cell poizoni: IL-12/18/21
Guia et al. anapeza kuti odwala omwe ali ndi vuto la IL-12Rbeta1 chifukwa cha kusintha kwa IL12RB1, NK cell subpopulation inachepetsedwa kwambiri, makamaka popanga IFN-γ; Deta yofananira idapezedwa kuchokera kwa odwala omwe adataya kwathunthu IL-12p40. Kuonjezera apo, chiwerengero cha zotsatira za kukumbukira T cell subpopulation kufotokoza CD56 kunachepetsedwa kwambiri kwa odwala omwe ali ndi vuto la IL-12Rbeta1 ndi IL-12p40. Chifukwa chake, ma cell a NK amunthu amafunikira IL-12 mu vivo kuti apeze kuyankha kwake kokwanira.

Chithunzi chojambula:Guia S, et al. Magazi. 2008

 

Mirjačić ndi al. adafufuza zotsatira za IL-12 ndi IL-18 pa ntchito ndi mawonekedwe a ma receptor a NK cell ndi magawo awo mwa odwala omwe ali ndi melanoma ya metastatic. Kuphatikizika kwa IL-12 ndi IL-18 mu m'galasi kungabweretse zotsatira zabwino pa NK cell toxicity ndi CD25 receptor expression kwa odwala metastatic melanoma.

Chithunzi chochokera: Mirjačić et al.. J Transl Med. 2015. PMID: 25889680.

 

Strengell M et al. inanenanso kuti synergistic zotsatira za IL-21 ndi IL-15 kapena IL-18 akhoza kupititsa patsogolo kupanga IFN- γ mu NK ndi T maselo a anthu, kuchita cytotoxic zotsatira.

chithunzi gwero:Strengell M, et al. J Immunol. 2003.

 

Beijing T&L Biotechnology Ltd., yakhala ikuyang'ana kwambiri pa R&D ndikupanga zida za GMP grade core reagent m'munda wa CGT kwazaka zopitilira khumi, ndikupereka mayankho athunthu asayansi yamoyo. Kampaniyo ili ndi nsanja za eukaryotic ndi prokaryotic protein expression engineering, nsanja zokulitsa ukadaulo wa cell Culture, komanso nsanja zopangira ma in vitro diagnostic reagent. Mapuloteni amtundu wa GMP omwe amapangidwanso amakhala ndi endotoxin yotsika, kuyera kwambiri, kuchita zinthu zambiri, komanso kusasinthasintha kwapakati pa batch. Nthawi yomweyo, zida za pure factor cell culture reagent zomwe zimaperekedwa zimakhala ndi activation yayikulu komanso kukulitsa bwino komanso magwiridwe antchito otsogola. Pakadali pano, zopangira zazikulu zamakampani monga zopangira mapuloteni ophatikizanso komanso mizere yopangira zida zamtundu wa cell zatha kumaliza kusungitsa kwa FDA DMF, komwe kumatha kukwaniritsa zosowa zamakasitomala olengeza mankhwala.

T&L imalimbikitsa NK cell culture product:

 

1. NK Culture Mapuloteni Ofunika: Mapuloteni aumunthu a IL-1β

Chithunzi cha 1: Recombinant Human IL-1β imathandizira kutulutsidwa kwa IFN-γ ndi NK-92 maselo achilengedwe amtundu wa lymphoma.

 

Recombinant munthu IL-12 mapuloteni

Chithunzi cha 2: Recombinant Human IL-12 imalimbikitsa kuchulukana kwa PBMC

 

Recombinant munthu IL-15 mapuloteni

Chithunzi 3: Recombinant Human IL-15 imalimbikitsa kuchulukana kwa CTLL-2

 

Recombinant munthu IL-18 mapuloteni

Chithunzi cha 4: Recombinant Human IL-18 imalimbikitsa kuchulukana kwa KG-1

 

Recombinant munthu IL-21 mapuloteni

Chithunzi cha 5: Mapuloteni aumunthu a IL-21 amathandizira katulutsidwe ka IFN- γ ndi NK-92

 

2. NK cell chikhalidwe zida

Kusintha kwa kuchuluka kwa maselo a NK

 

Kusintha kwa ma cell a NK

 

NK chiŵerengero cha kukula kwa maselo

 

Za T&L
T&L Biotechnology Ltd., yomwe idakhazikitsidwa mchaka cha 2011, imayang'ana kwambiri kafukufuku ndi chitukuko cha zida za GMP zopangira ma cell and gene therapy (CGT). Timadzipereka kupereka zinthu zodalirika ndi ntchito za sayansi ya moyo