One-step mixing with humanized anti-mPEG bispecific antibody enhances tumor accumulation and therapeutic efficacy of mPEGylated nanoparticles

Kao, Chien-Han; Wang, Jaw‐Yuan; Chuang, Kai‐Hsiang; Chuang, Chih Hung; Cheng, Tian‐Lu; Hsieh, Yuan-Chin; Tseng, Yun Long; Chen, Bing Mae; Roffler, Steve R.; Tian, Chen

doi:10.1016/j.biomaterials.2014.08.032

Cited by 48 publications

(50 citation statements)

References 49 publications

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“…To help overcome these problems, Brinkmann and colleagues developed bispecific digoxigenin-binding antibodies for delivery of digoxigen-modified nanocarriers to disease sites3839. Likewise, we previously described bispecific PEG-binding antibodies for tumour-specific delivery of PEGylated compounds4041. However, direct attachment of targeting ligands to nanocarriers can reduce the stealth feature of the nanocarriers, resulting in accelerated clearance and reduced uptake into tumours10.…”

Section: Discussionmentioning

confidence: 99%

Conditional internalization of PEGylated nanomedicines by PEG engagers for triple negative breast cancer therapy

Burnouf

Chuang

et al. 2017

Nat Commun

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Triple-negative breast cancer (TNBC) lacks effective treatment options due to the absence of traditional therapeutic targets. The epidermal growth factor receptor (EGFR) has emerged as a promising target for TNBC therapy because it is overexpressed in about 50% of TNBC patients. Here we describe a PEG engager that simultaneously binds polyethylene glycol and EGFR to deliver PEGylated nanomedicines to EGFR+ TNBC. The PEG engager displays conditional internalization by remaining on the surface of TNBC cells until contact with PEGylated nanocarriers triggers rapid engulfment of nanocargos. PEG engager enhances the anti-proliferative activity of PEG-liposomal doxorubicin to EGFR+ TNBC cells by up to 100-fold with potency dependent on EGFR expression levels. The PEG engager significantly increases retention of fluorescent PEG probes and enhances the antitumour activity of PEGylated liposomal doxorubicin in human TNBC xenografts. PEG engagers with specificity for EGFR are promising for improved treatment of EGFR+ TNBC patients.

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Section: Discussionmentioning

confidence: 99%

Conditional internalization of PEGylated nanomedicines by PEG engagers for triple negative breast cancer therapy

Burnouf

Chuang

et al. 2017

Nat Commun

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“…In contrast with our previously described anti-methoxy-PEG BsAb fragments (26), here, we investigated intact IgG 1 hybrid antibodies that bind to the ethylene oxide backbone of PEG. One potential advantage of human IgG 1 hybrid antibodies is the opportunity for both targeted delivery of therapeutic agents and induction of anticancer immune responses.…”

Section: Discussionmentioning

confidence: 99%

Selective Delivery of PEGylated Compounds to Tumor Cells by Anti-PEG Hybrid Antibodies

Tung

Chen

et al. 2015

Molecular Cancer Therapeutics

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“…A bispecific fragment composed of anti-mPEG Fab and anti-EGFR or anti-HER2 scFv was combined with mPEG-conjugated nanoparticles carrying a fluorescent dye, an MRI contrast, or liposomal doxorubicin. The anti-mPEG portion of the fragment increased accumulation of the nanoparticles in tumors and enhanced optical or MRI tumor imaging as well as anti-tumor drug efficacy (Kao et al, 2014). …”

Section: Development Of Antibodies and Fragments For In Vivo Imagingmentioning

confidence: 99%

In vivo imaging with antibodies and engineered fragments

Freise

2015

Molecular Immunology

177

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Antibodies have clearly demonstrated their utility as therapeutics, providing highly selective and effective drugs to treat diseases in oncology, hematology, cardiology, immunology and autoimmunity, and infectious diseases. More recently, a pressing need for equally specific and targeted imaging agents for assessing disease in vivo, in preclinical models and patients, has emerged. This review summarizes strategies for developing and optimizing antibodies as targeted probes for use in non-invasive imaging using radioactive, optical, magnetic resonance, and ultrasound approaches. Recent advances in engineered antibody fragments and scaffolds, conjugation and labeling methods, and multimodality probes are highlighted. Importantly, antibody-based imaging probes are seeing new applications in detection and quantitation of cell surface biomarkers, imaging specific responses to targeted therapies, and monitoring immune responses in oncology and other diseases. Antibody-based imaging will provide essential tools to facilitate the transition to truly precision medicine.

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One-step mixing with humanized anti-mPEG bispecific antibody enhances tumor accumulation and therapeutic efficacy of mPEGylated nanoparticles

Cited by 48 publications

References 49 publications

Conditional internalization of PEGylated nanomedicines by PEG engagers for triple negative breast cancer therapy

Conditional internalization of PEGylated nanomedicines by PEG engagers for triple negative breast cancer therapy

Selective Delivery of PEGylated Compounds to Tumor Cells by Anti-PEG Hybrid Antibodies

In vivo imaging with antibodies and engineered fragments

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