Site-specific PEGylation of an anti-CEA/CD3 bispecific antibody improves its antitumor efficacy

Liu, Jiayu; Deng, Wentong; Xing, Jieyu; Li, Qing; Wang, Zhong

doi:10.2147/ijn.s164542

Cited by 27 publications

(26 citation statements)

References 46 publications

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“…One of these is extending the serum half-life of the nanobody using different formatting options. Examples hereof are fusion of the nanobody directly with albumin, polyethylene glycol (PEG; PEGylation) or IgG-Fc (allowing recycling through the neonatal Fc receptor [FcR]), or indirectly with a second nanobody that binds albumin or the neonatal FcR, thereby generating bispecific constructs 39-42. Another option to obtain maximal delivery in the tumor site is to use a gene therapy approach, which could be highly feasible for nanobodies as these are simple proteins expressed from one single gene 43,44.…”

Section: Advantages and Disadvantages Of Nanobodiesmentioning

confidence: 99%

Theranostics in immuno-oncology using nanobody derivatives

Lecocq

Vlaeminck

Hanssens³

et al. 2019

Theranostics

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Targeted therapy and immunotherapy have become mainstream in cancer treatment. However, only patient subsets benefit from these expensive therapies, and often responses are short‐lived or coincide with side effects. A growing modality in precision oncology is the development of theranostics, as this enables patient selection, treatment and monitoring. In this approach, labeled compounds and an imaging technology are used to diagnose patients and select the best treatment option, whereas for therapy, related compounds are used to target cancer cells or the tumor stroma. In this context, nanobodies and nanobody-directed therapeutics have gained interest. This interest stems from their high antigen specificity, small size, ease of labeling and engineering, allowing specific imaging and design of therapies targeting antigens on tumor cells, immune cells as well as proteins in the tumor environment. This review provides a comprehensive overview on the state-of-the-art regarding the use of nanobodies as theranostics, and their importance in the emerging field of personalized medicine.

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Section: Advantages and Disadvantages Of Nanobodiesmentioning

confidence: 99%

Theranostics in immuno-oncology using nanobody derivatives

Lecocq

Vlaeminck

Hanssens³

et al. 2019

Theranostics

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“…The serum samples were collected at 0.25, 0.5, 1, 2, 4, 8, 12, 24, and 48 h post-injection for bioanalytical measurement. Antibody concentrations in serum were determined by the ELISA method, as described previously 45 . PK analyses were performed according to standard non-compartmental analysis using Kinetica (version [v.]5.1 SP1, Thermo Fisher Scientific).…”

Section: Methodsmentioning

confidence: 99%

Bp-Bs, a Novel T-cell Engaging Bispecific Antibody with Biparatopic Her2 Binding, Has Potent Anti-tumor Activities

Liu

Lin

et al. 2019

Molecular Therapy - Oncolytics

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Patients with Human epidermal growth factor receptor type 2 (Her2) overexpression are associated with aggressive tumor growth and poor clinical outcomes. Bispecific antibodies targeting Her2 have recently exhibited potent effects on Her2 signal inhibition. In this study, a novel biparatopic anti-Her2 bispecific antibody (Bp-Bs) was constructed by linking a single anti-CD3 Fab with two different anti-Her2 single-domain antibodies targeting non-overlapping epitopes of Her2. The Bp-Bs demonstrated strong binding on Her2-positive cells and potent cytotoxicity on Her2-positive tumor cells, even Her2-low expression cells, suggesting that biparatopic bispecific antibodies may have improved therapeutic benefits on broad Her2 patient populations.

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“…Li et al ( 96 ) created a BiTE composed of an anti-CEA nanobody and anti-CD3 Fab (“S-Fab”), with significant T-cell mediated cytotoxicity in vitro and in vivo . The S-Fab was PEGylated to extend its serum half-life and reported uncompromised anti-tumor activity ( 97 ). Various advancements have also been made in targeting CD3 ( 98 ), and anti-CD3 nanobodies have recently reported a targeted anti-tumor response in vivo ( 93 , 99 ).…”

Section: Nanobodies: Synergy With Other Cancer Therapeuticsmentioning

confidence: 99%

Nanobodies: Next Generation of Cancer Diagnostics and Therapeutics

2020

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The development of targeted medicine has greatly expanded treatment options and spurred new research avenues in cancer therapeutics, with monoclonal antibodies (mAbs) emerging as a prevalent treatment in recent years. With mixed clinical success, mAbs still hold significant shortcomings, as they possess limited tumor penetration, high manufacturing costs, and the potential to develop therapeutic resistance. However, the recent discovery of “nanobodies,” the smallest-known functional antibody fragment, has demonstrated significant translational potential in preclinical and clinical studies. This review highlights their various applications in cancer and analyzes their trajectory toward their translation into the clinic.

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Site-specific PEGylation of an anti-CEA/CD3 bispecific antibody improves its antitumor efficacy

Cited by 27 publications

References 46 publications

Theranostics in immuno-oncology using nanobody derivatives

Theranostics in immuno-oncology using nanobody derivatives

Bp-Bs, a Novel T-cell Engaging Bispecific Antibody with Biparatopic Her2 Binding, Has Potent Anti-tumor Activities

Nanobodies: Next Generation of Cancer Diagnostics and Therapeutics

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