Explicyte’s expertise and advanced technologies have been harnessed so as to build a cell-based service platform for immuno-oncology (IO) assessment and drug discovery.
Being sensitive, quantitative, and high throughput-compatible, our assays are not solely based on the analysis of phenotypic parameters to assess the immune response, but also consist in measuring an array of cytokines – pro- or anti-inflammatory – directly underlying the specific response of every immune cell subsets. Measurements of these cytokines in our various in vitro IO cell-based assays constitute relevant surrogates to evaluate therapeutics for their modulatory potential of immune cell functions.
1. PBMC release of key inflammatory cytokines is induced upon CD3 activation and further optimized by immune checkpoint inhibitors
Key inflammatory cytokines i.e. TNF𝞪 (A), IL2 (B), and IFN𝞬 (C) are shown to be differentially modulated upon stimulation of PBMCs with increasing concentrations of anti-CD3 antibody. While TNFa secretion is efficiently induced at 24h (gray bars) compared to 72h (red bars), released IFNg and IL2 levels are time- and dose-dependently increased following anti-CD3 treatment (24h in gray and 72h in red). Cytokine quantification, especially IL2 and IFNg quantified by HTRF, appears valuable surrogate tools to ascertain the PBMC activation. Furthermore, treatment of anti-CD3-activated PBMC with increasing concentrations of each of anti-PD1 antibodies (Nivolumab or Pembrolizumab) leads to a significant dose-dependent increase of IFNg release (D), thereby reflecting further optimization of PBMC activation.
2. T cell IFN𝜸 release is induced in a MLR assay and further optimized by immune checkpoint inhibitors
Our robust and high throughput human allogeneic mixed lymphocyte reaction (MLR) assay consists in a co-culture of CD4+ T cells (responder) with monocyte-derived Dendritic Cells (stimulator). Measurement of released IFNγ constitutes an accurate surrogate to investigate novel immunotherapeutics capable of enhancing DC-mediated T cell activation.
In our assay, isolated peripheral blood monocytes from six human donors are differentiated into mDC and mixed with T CD4+ cells each isolated from different donors (A). IFNg levels released in the supernatants are measured after 72h using a specific HTRF-based specific kit. While displaying an expected response amplitude in IFN𝜸 release varying from a donor pair to another one, the MLR response is robust and is further optimized following PD1 blockade. More thoroughly, PD1/PDL1 blockade dose dependently optimize the MLR response, as highlighted through the dose-dependent promotion of IFN𝜸 release by anti-PD1 (Nivolumab and Pembrolizumab) and anti-PDL1 (Atezolizumab) antibodies , measured after 72h in our allogeneic MLR assay (B).
3. IFN𝜸 release by activated NK cells is induced against tumor cells and is optimized by anti-tumor antigen antibodies
In our NK cell-mediated killing assay, we are used to measure the IFN𝜸 release as a functionally relevant surrogate of the NK cell activity / activation to evaluate the efficacy of i) therapeutics in enhancing the NK cell killing ability and of ii) candidate antibodies targeting specific tumor antigens in eliciting an antibody-dependent NK cell cytotoxicity (ADCC) activity.
SKOV3 ovarian (A, HER2+) and A549 lung (B, HER2-) tumor cells were cultured under control or Trastuzumab (increasing doses)-treated conditions and, IL2- activated primary NK cells were then added at different E:T ratios. 24h later, supernatants were collected and analyzed for IFN𝞬 release as a surrogate of NK-induced cell toxicity. While IFN𝞬 levels are increased in a NK ratio-dependent manner, thereby reflecting the basal direct NK cytotoxic activity on both SKOV3 and A549 cells (A, B), Trastuzumab treatment of tumor cells is shown to further promote this increase only with SKOV3 cells (A, HER2+), whatever the E:T ratio, in a NK ratio-dependent and dose-dependent way, thereby showing an ADCC activity.
4. M2 macrophage phenotype and its mediated T cell response immunosuppression are reversed by molecular pathway modulators and immune checkpoint inhibitors
M2 macrophages are known to display a IL6low IL10high profile, a phenotype known to be underpinned by ‘’overactivated’’ signaling pathways in these cells, such as JAK/STAT and SMAD/p38 MAPK, and to be therefore involved in their T cell response suppression function.
Addition of a p38 MAPK inhibitor during the M2 polarization process is shown to be capable of repolarizing/switching M2 phenotype by reverting, at least partially but dose-dependently, the IL6low IL10high profile (A). In the co-culture immunosuppression assay with PBMCs (B), M2 macrophages exhibit a strong suppression of T cell activity shown through released IFNg level decrease. M2 suppression function is known to be exerted via multiple mechanisms including PD1/PDL1 axis engagement or pathway modulation, among other ways. Interestingly, co-cultures of activated PBMC with M2 macrophages that underwent treatment with a p38 MAPK inhibitor during their polarization result, at least partially, in a dose-dependent reversal of the T cell activation suppression compared to untreated PBMC/M2 co-cultures. Atezolizumab treatment of co-cultures is also shown to completely and dose-dependently relieve the immunosuppressive M2 function on T cell response, with a reversal of the M2 IFNg release profile.
проститутки нижнего новгорода
путаны спб
проститутки иркутск 2
индивидуалки иркутск на выезд
объявления интим иркутск
шлюхи город иркутск
1xbet com login in
https://khelraja-india.com/download-app/
I know a lot of folks whom I think would really enjoy your content that covers in depth. I just hope you wouldn’t mind if I share your blog to our community. Thanks, and feel free to surf my website 59N for content about Cosmetics.
Impressive posts! My blog FQ5 about Thai-Massage also has a lot of exclusive content I created myself, I am sure you won’t leave empty-handed if you drop by my page.
With your post, your readers, particularly those beginners who are trying to explore this field won’t leave your page empty-handed. Here is mine at 57N I am sure you’ll gain some useful information about Cosmetics too.
https://runpost.com.in/discover-the-ultimate-betting-experience-with-the-1xbet-app/
An interesting topic and I’m glad to come across your page where I found some helpful insights. Check out my website QH8 too, if you need additional resources about Car Purchase.
I confirm. It was and with me.
https://onecooldir.1directory.org/details.php?id=276303
https://virtual-local-numbers.com/countries/1240-india-toll-free-numbers.html
reddit where buy priligy Your breast cancer treatment should be highly personalized to your needs
https://apostrof.com.ua/rizne/vyrobnycztvo-dymohidnyh-ta-ventylyaczijnyh-system-suchasni-rishennya-vid-glemanlas/
https://my.desktopnexus.com/lamborghinidubai/
https://geo.hosting/
https://pq.hosting/dedicated-server-great-britain
https://www.speedrun.com/users/findytripcom
https://car-rental-sharjah.com/
buy propecia online india in 2007, neither the VA doctor nor the nurse who administered this offered any info on side effects
https://continent-telecom.com/virtual-number-germany
https://athens-rentalcars.com/ru/
Completely I share your opinion. In it something is also idea excellent, I support.
farmaci senza ricetta elenco: Farma Prodotti – Farmacia online piГ№ conveniente
acquisto farmaci con ricetta
Excuse, that I interrupt you, there is an offer to go on other way.
https://farmatadalitaly.shop/# farmaci senza ricetta elenco
Farmacie on line spedizione gratuita
Poker rooms host exciting tournaments regularly.: taya365 login – taya365.art
winchile [url=http://winchile.pro/#]win chile[/url] Las experiencias son Гєnicas en cada visita.
https://jugabet.xyz/# La competencia entre casinos beneficia a los jugadores.
The thrill of winning keeps players engaged.
The Philippines has a vibrant nightlife scene. https://winchile.pro/# Los jackpots progresivos atraen a los jugadores.
Many casinos provide shuttle services for guests.: taya365 – taya365 com login
Visitors come from around the world to play.: phmacao.life – phmacao com
https://jugabet.xyz/# La pasiГіn por el juego une a personas.
The casino scene is constantly evolving.
Many casinos host charity events and fundraisers. https://phmacao.life/# Manila is home to many large casinos.
phmacao com login [url=http://phmacao.life/#]phmacao[/url] Many casinos host charity events and fundraisers.
п»їLos casinos en Chile son muy populares.: jugabet.xyz – jugabet casino
The ambiance is designed to excite players.: phmacao com – phmacao casino
https://phtaya.tech/# Online gaming is also growing in popularity.
The poker community is very active here.
The casino atmosphere is thrilling and energetic. https://phtaya.tech/# Casino visits are a popular tourist attraction.
п»їCasinos in the Philippines are highly popular.: phtaya login – phtaya
http://phtaya.tech/# A variety of gaming options cater to everyone.
Promotions are advertised through social media channels.
phmacao casino [url=https://phmacao.life/#]phmacao[/url] Some casinos feature themed gaming areas.
http://winchile.pro/# Los casinos son lugares de reuniГіn social.
Many casinos host charity events and fundraisers.
п»їCasinos in the Philippines are highly popular.: taya777 app – taya777 register login
A variety of gaming options cater to everyone.: phtaya – phtaya casino
http://phmacao.life/# The Philippines offers a rich gaming culture.
Gambling can be a social activity here.
Casinos offer delicious dining options on-site. https://winchile.pro/# La mГєsica acompaГ±a la experiencia de juego.
Slot machines attract players with big jackpots.: phtaya – phtaya.tech
phmacao [url=http://phmacao.life/#]phmacao com[/url] The casino experience is memorable and unique.
https://jugabet.xyz/# La adrenalina es parte del juego.
Casinos offer delicious dining options on-site.
Without conversations!
Many casinos offer luxurious amenities and services. https://taya365.art/# Gambling can be a social activity here.
Los casinos organizan eventos especiales regularmente.: winchile – winchile.pro
The thrill of winning keeps players engaged.: taya365 – taya365.art
https://taya777.icu/# Gambling can be a social activity here.
Manila is home to many large casinos.
Promotions are advertised through social media channels. http://winchile.pro/# La Г©tica del juego es esencial.
Los jackpots progresivos atraen a los jugadores.: winchile – win chile
https://phmacao.life/# п»їCasinos in the Philippines are highly popular.
Entertainment shows are common in casinos.
taya777 app [url=https://taya777.icu/#]taya777[/url] Security measures ensure a safe environment.
Many casinos host charity events and fundraisers.: taya777 login – taya777.icu
http://jugabet.xyz/# Hay reglas especГficas para cada juego.
Online gaming is also growing in popularity.
Live dealer games enhance the casino experience. https://phtaya.tech/# Gaming regulations are overseen by PAGCOR.
Responsible gaming initiatives are promoted actively.: taya365 login – taya365 login
Los pagos son rГЎpidos y seguros.: jugabet – jugabet chile
https://phtaya.tech/# Many casinos have beautiful ocean views.
The ambiance is designed to excite players.
win chile [url=http://winchile.pro/#]winchile casino[/url] Los juegos en vivo ofrecen emociГіn adicional.
Loyalty programs reward regular customers generously. http://phmacao.life/# High rollers receive exclusive treatment and bonuses.
Some casinos feature themed gaming areas.: phtaya login – phtaya.tech
http://taya777.icu/# Some casinos feature themed gaming areas.
Players can enjoy high-stakes betting options.
Las apuestas mГnimas son accesibles para todos.: winchile.pro – winchile
https://phmacao.life/# Security measures ensure a safe environment.
Most casinos offer convenient transportation options.
Los jugadores disfrutan del pГіker en lГnea.: winchile casino – win chile
jugabet casino [url=http://jugabet.xyz/#]jugabet chile[/url] La variedad de juegos es impresionante.
Slot machines feature various exciting themes. https://jugabet.xyz/# La iluminaciГіn crea un ambiente vibrante.
Many casinos provide shuttle services for guests.: phmacao com – phmacao com
https://phmacao.life/# Casinos often host special holiday promotions.
Live dealer games enhance the casino experience.
Cashless gaming options are becoming popular.: taya777 register login – taya777 register login
https://taya365.art/# The gaming floors are always bustling with excitement.
High rollers receive exclusive treatment and bonuses.
Security measures ensure a safe environment.: taya365 – taya365.art
Las promociones de fin de semana son populares.: jugabet – jugabet
https://taya365.art/# The Philippines offers a rich gaming culture.
Casinos offer delicious dining options on-site.
jugabet [url=https://jugabet.xyz/#]jugabet casino[/url] La historia del juego en Chile es rica.
La Г©tica del juego es esencial.: jugabet.xyz – jugabet chile
La competencia entre casinos beneficia a los jugadores.: winchile – winchile
http://winchile.pro/# Los casinos ofrecen entretenimiento en vivo.
Players can enjoy high-stakes betting options.
I think, you will come to the correct decision. Do not despair.
п»їLos casinos en Chile son muy populares.: winchile.pro – winchile
https://taya777.icu/# Cashless gaming options are becoming popular.
Players can enjoy high-stakes betting options.
Players can enjoy high-stakes betting options.: taya777 – taya777 register login
taya365 com login [url=http://taya365.art/#]taya365[/url] Manila is home to many large casinos.
https://winchile.pro/# Es comГєn ver jugadores sociales en mesas.
The casino atmosphere is thrilling and energetic.
Players enjoy a variety of table games.: phtaya login – phtaya
Most casinos offer convenient transportation options.: taya365.art – taya365
https://taya777.icu/# Manila is home to many large casinos.
Some casinos feature themed gaming areas.
Security measures ensure a safe environment. https://winchile.pro/# Las apuestas deportivas tambiГ©n son populares.
taya777 login [url=http://taya777.icu/#]taya777 login[/url] Some casinos have luxurious spa facilities.
Casino visits are a popular tourist attraction.: taya777 app – taya777
https://jugabet.xyz/# п»їLos casinos en Chile son muy populares.
Security measures ensure a safe environment.
Gaming regulations are overseen by PAGCOR.: phtaya login – phtaya
http://phmacao.life/# Visitors come from around the world to play.
Promotions are advertised through social media channels.
A variety of gaming options cater to everyone.: taya777.icu – taya777 register login
The Philippines has several world-class integrated resorts. https://phmacao.life/# Loyalty programs reward regular customers generously.
http://winchile.pro/# Las promociones atraen nuevos jugadores diariamente.
Manila is home to many large casinos.
phtaya [url=https://phtaya.tech/#]phtaya.tech[/url] Players enjoy a variety of table games.
Las experiencias son Гєnicas en cada visita.: jugabet chile – jugabet.xyz
Some casinos feature themed gaming areas.: phmacao club – phmacao com
https://jugabet.xyz/# La iluminaciГіn crea un ambiente vibrante.
The gaming floors are always bustling with excitement.
The casino atmosphere is thrilling and energetic.: taya365 – taya365 login
High rollers receive exclusive treatment and bonuses.: phtaya.tech – phtaya
http://phtaya.tech/# Online gaming is also growing in popularity.
The poker community is very active here.
taya365 [url=http://taya365.art/#]taya365.art[/url] Casino visits are a popular tourist attraction.
MegaIndiaPharm: top online pharmacy india – best india pharmacy
cheapest pharmacy for prescription drugs https://familypharmacy.company/# Online pharmacy USA
discount drugs [url=https://discountdrugmart.pro/#]mail order pharmacy no prescription[/url] discount drug mart
online pharmacy no prescription https://discountdrugmart.pro/# discount drug mart pharmacy
Mega India Pharm: best india pharmacy – india pharmacy
discount drug pharmacy: drugmart – drug mart
canadian online pharmacy no prescription https://xxlmexicanpharm.com/# mexican rx online
canadian pharmacy no prescription https://familypharmacy.company/# online pharmacy delivery usa
no prescription needed canadian pharmacy [url=https://discountdrugmart.pro/#]drug mart[/url] discount drug pharmacy
top 10 online pharmacy in india: india pharmacy mail order – MegaIndiaPharm
online pharmacy delivery usa: rx pharmacy no prescription – family pharmacy
canada pharmacy coupon https://easycanadianpharm.com/# easy canadian pharm
online pharmacy discount code https://xxlmexicanpharm.shop/# reputable mexican pharmacies online
no prescription pharmacy paypal http://easycanadianpharm.com/# buying drugs from canada
canadian valley pharmacy: easy canadian pharm – canadian pharmacies that deliver to the us
prescription drugs from canada https://easycanadianpharm.shop/# easy canadian pharm
discount drug mart [url=https://discountdrugmart.pro/#]drugmart[/url] online pharmacy no prescription
Best online pharmacy: Cheapest online pharmacy – no prescription needed pharmacy
rxpharmacycoupons https://xxlmexicanpharm.com/# mexican mail order pharmacies
discount drug pharmacy: discount drug pharmacy – discount drug mart pharmacy
prescription drugs online https://familypharmacy.company/# canada pharmacy not requiring prescription
MegaIndiaPharm: MegaIndiaPharm – MegaIndiaPharm
pharmacy no prescription required https://familypharmacy.company/# Online pharmacy USA
cheapest pharmacy for prescriptions without insurance: canadian pharmacy coupon code – drug mart
MegaIndiaPharm [url=http://megaindiapharm.com/#]MegaIndiaPharm[/url] MegaIndiaPharm
reputable online pharmacy no prescription https://easycanadianpharm.shop/# easy canadian pharm
discount drug pharmacy: discount drug mart – discount drug mart pharmacy
canada drugs coupon code https://easycanadianpharm.com/# canadian pharmacy mall
xxl mexican pharm: xxl mexican pharm – mexico pharmacies prescription drugs
online pharmacy prescription https://easycanadianpharm.com/# legitimate canadian pharmacies
xxl mexican pharm: п»їbest mexican online pharmacies – xxl mexican pharm
canadian pharmacy without prescription https://megaindiapharm.com/# Mega India Pharm
rx pharmacy no prescription http://xxlmexicanpharm.com/# mexican rx online
mexico drug stores pharmacies [url=http://xxlmexicanpharm.com/#]xxl mexican pharm[/url] mexican mail order pharmacies
xxl mexican pharm: medicine in mexico pharmacies – п»їbest mexican online pharmacies
pharmacy online 365 discount code https://discountdrugmart.pro/# discount drug pharmacy
canadian pharmacy no prescription needed https://megaindiapharm.shop/# MegaIndiaPharm
canadian pharmacy coupon https://discountdrugmart.pro/# drug mart
discount drug mart pharmacy: discount drug pharmacy – discount drug mart
online pharmacy delivery usa: Online pharmacy USA – canadian pharmacies not requiring prescription
canadian online pharmacy no prescription http://discountdrugmart.pro/# discount drug pharmacy
easy canadian pharm [url=https://easycanadianpharm.com/#]easy canadian pharm[/url] canadian pharmacy prices
rx pharmacy no prescription https://familypharmacy.company/# cheapest pharmacy for prescriptions
MegaIndiaPharm: Mega India Pharm – best india pharmacy
rxpharmacycoupons http://familypharmacy.company/# Online pharmacy USA
cheapest online pharmacy india: top 10 online pharmacy in india – buy prescription drugs from india
online pharmacy prescription https://easycanadianpharm.shop/# the canadian pharmacy
Cheapest online pharmacy: canadian pharmacy world coupon – Online pharmacy USA
cheapest pharmacy to fill prescriptions with insurance https://familypharmacy.company/# cheapest pharmacy to fill prescriptions with insurance
MegaIndiaPharm: Mega India Pharm – india pharmacy
buy medicines online in india [url=https://megaindiapharm.com/#]Mega India Pharm[/url] MegaIndiaPharm
online canadian pharmacy coupon https://megaindiapharm.com/# indian pharmacy online
legit non prescription pharmacies https://xxlmexicanpharm.com/# mexican online pharmacies prescription drugs
family pharmacy: online pharmacy delivery usa – Online pharmacy USA
no prescription needed canadian pharmacy https://easycanadianpharm.com/# pharmacy rx world canada
discount drug pharmacy: discount drug pharmacy – discount drug mart
online pharmacy without prescription https://discountdrugmart.pro/# discount drugs
cheapest pharmacy for prescription drugs http://discountdrugmart.pro/# discount drug pharmacy
mail order pharmacy no prescription http://megaindiapharm.com/# Mega India Pharm
Online pharmacy USA: family pharmacy – canadian pharmacy no prescription needed
discount drug pharmacy: drug mart – discount drug mart pharmacy
uk pharmacy no prescription https://easycanadianpharm.com/# canadian pharmacy mall
uk pharmacy no prescription http://familypharmacy.company/# online pharmacy delivery usa
xxl mexican pharm [url=http://xxlmexicanpharm.com/#]mexican drugstore online[/url] mexican rx online
indian pharmacy: indian pharmacy online – top online pharmacy india
Best online pharmacy: reputable online pharmacy no prescription – no prescription needed pharmacy
online pharmacy discount code https://xxlmexicanpharm.com/# pharmacies in mexico that ship to usa
best canadian pharmacy no prescription http://discountdrugmart.pro/# drug mart
canadian pharmacy store: pharmacy canadian superstore – easy canadian pharm
cheapest pharmacy to get prescriptions filled https://megaindiapharm.shop/# Mega India Pharm
canadian pharmacy no prescription needed https://megaindiapharm.shop/# Mega India Pharm
india pharmacy [url=https://megaindiapharm.com/#]Mega India Pharm[/url] online shopping pharmacy india
canadian pharmacy world coupon https://megaindiapharm.com/# pharmacy website india
online pharmacy delivery usa: family pharmacy – Cheapest online pharmacy
canadian pharmacies that deliver to the us: maple leaf pharmacy in canada – easy canadian pharm
no prescription pharmacy paypal http://familypharmacy.company/# online pharmacy delivery usa
pharmacy online 365 discount code http://xxlmexicanpharm.com/# xxl mexican pharm
discount drug pharmacy: online pharmacy no prescription – discount drug pharmacy
rx pharmacy coupons http://discountdrugmart.pro/# discount drug mart pharmacy
canadian pharmacy world coupon code https://xxlmexicanpharm.com/# xxl mexican pharm
MegaIndiaPharm [url=https://megaindiapharm.com/#]top online pharmacy india[/url] Mega India Pharm
Mega India Pharm: best india pharmacy – reputable indian pharmacies
online pharmacy prescription http://megaindiapharm.com/# MegaIndiaPharm
online pharmacy non prescription drugs http://megaindiapharm.com/# Mega India Pharm