One target, different effects: a comparison of distinct therapeutic antibodies against the same targets

Shim, Hyunbo

doi:10.3858/emm.2011.43.10.063

Cited by 56 publications

(53 citation statements)

References 85 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Özetle infliksimab (IFX), adalimumab (ADA), golimumab (GOL), sertolizumab (CZP) ve etanersept (ETA) TNF-α inhibisyonu yapan biyolojik tedavi ajanlar›d›r. [3,4] Anakinra, kanakinumab ve rilonasept ise IL-1β inhibisyonu yapan biyolojik tedavi ajanlar›d›r. [5] Di¤er yandan, tosilizumab (TCZ) IL-6 reseptörü (IL-6R) üzerinden IL-6 inhibisyonu yaparak etkili olan bir biyolojik ajand›r.…”

Section: Biyolojik Tedavi Ajanlar› Etkilerini Nas›l Göstermektedir?unclassified

“…Böylece, immün kompleks oluflumunu ve dolay›s›yla nötrofil degranülasyonu ve süperoksit oluflumunu azalt›r. [3,4] CZP'nin in-vitro ortamda insan TNF-α için afinitesi yüksektir; ortalama ayr›flma sabiti olarak bilinen KD de¤eri di¤er monoklonallerden daha düflüktür. CZP farmakokineti¤i yafl, cinsiyet, ›rk ve hafif renal yetmezlikten etkilenmemektedir.…”

Section: Raedunclassified

“…Di¤er anti-TNF ajanlara benzer flekilde, CZP'nin de MTX ile birlikte verilmesi durumunda anti-ilaç antikor s›kl›¤›n›n daha düflük oldu¤u ve CZP terapötik plazma düzeyleri-nin daha iyi korundu¤u da gösterilmifltir. [3,4] CZP eriflkin dozu s›f›r›nc›, ikinci ve dördüncü haftada 400 mg ve sonra her iki haftada bir 200 mg SK enjeksiyondur. [4,18] Pegilasyon nedir?…”

Section: Raedunclassified

“…Böylece, nötrofil degranülasyonu ve reaktif oksijen radikal üretiminde art›fl gibi sekonder problemlerin de önüne geçilmifl olur. [3,4,18] Monoklonal anti-TNF ajanlar›n farmakolojik olarak etanersepte göre daha güçlü TNF inhibisyonu yapmalar›n›n avantaj ve dezavanlajlar› var m›d›r?…”

Section: Raedunclassified

See 3 more Smart Citations

Biological treatments

Gülbezer¹,

Keser²

2017

RAED Derg

View full text Add to dashboard Cite

Section: Biyolojik Tedavi Ajanlar› Etkilerini Nas›l Göstermektedir?unclassified

Section: Raedunclassified

See 2 more Smart Citations

Biological treatments

Gülbezer¹,

Keser²

2017

RAED Derg

View full text Add to dashboard Cite

“…In contrast, because of their poor cellular membrane permeability, the targets of antibody drugs are currently limited to extracellular molecules. 2) Cell-penetrating peptides (CPPs) have been broadly used in vitro as a carrier to deliver cargoes into cells. Most are rich in basic amino acid residues, which allows them to interact with negatively charged glycosaminoglycan chains on the cellular membrane, followed by uptake into cells majorly via endocytosis/micropinocytosis.…”

mentioning

confidence: 99%

Cellular Uptake of IgG Using Collagen-Like Cell-Penetrating Peptides

Masuda

Yamamoto

Koide

2016

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Cell-penetrating peptides (CPPs) are attractive tools for delivering macromolecules that have poor membrane permeability, such as antibodies, into cells. However, the major drawback of conventional CPPs is their instability in bodily fluids. We previously reported a novel CPP employing a collagen-like triple-helical structure that exhibited remarkable resistance against serum proteases. Herein, we report the delivery of full-length immunoglobulin G (IgG) antibody into cells using a triple-helical CPP. The CPP was conjugated to IgG via a one-pot reaction using 2-iminothiolane as a crosslinking reagent. The triple-helical CPP was less prone to being aggregated and neutralized by serum than was octaarginine, a conventional CPP. However, most of the conjugates were found to be entrapped in endosomes.

show abstract

Quantitative modeling predicts competitive advantages of a next generation anti‐NKG2A monoclonal antibody over monalizumab for the treatment of cancer

Spinosa

Musial-Siwek

Presler

et al. 2021

CPT Pharmacom & Syst Pharma

View full text Add to dashboard Cite

A semimechanistic pharmacokinetic (PK)/receptor occupancy (RO) model was constructed to differentiate a next generation anti‐NKG2A monoclonal antibody (KSQ mAb) from monalizumab, an immune checkpoint inhibitor in multiple clinical trials for the treatment of solid tumors. A three‐compartment model incorporating drug PK, biodistribution, and NKG2A receptor interactions was parameterized using monalizumab PK, in vitro affinity measurements for both monalizumab and KSQ mAb, and receptor burden estimates from the literature. Following calibration against monalizumab PK data in patients with rheumatoid arthritis, the model successfully predicted the published PK and RO observed in gynecological tumors and in patients with squamous cell carcinoma of the head and neck. Simulations predicted that the KSQ mAb requires a 10‐fold lower dose than monalizumab to achieve a similar RO over a 3‐week period following q3w intravenous (i.v.) infusion dosing. A global sensitivity analysis of the model indicated that the drug‐target binding affinity greatly affects the tumor RO and that an optimal affinity is needed to balance RO with enhanced drug clearance due to target mediated drug disposition. The model predicted that the KSQ mAb can be dosed over a less frequent regimen or at lower dose levels than the current monalizumab clinical dosing regimen of 10 mg/kg q2w. Either dosing strategy represents a competitive advantage over the current therapy. The results of this study demonstrate a key role for mechanistic modeling in identifying optimal drug parameters to inform and accelerate progression of mAb to clinical trials.

show abstract

One target, different effects: a comparison of distinct therapeutic antibodies against the same targets

Cited by 56 publications

References 85 publications

Biological treatments

Biological treatments

Cellular Uptake of IgG Using Collagen-Like Cell-Penetrating Peptides

Quantitative modeling predicts competitive advantages of a next generation anti‐NKG2A monoclonal antibody over monalizumab for the treatment of cancer

Contact Info

Product

Resources

About