Multifunctional receptor-targeting antibodies for cancer therapy

Zhu, Yu; Choi, Sung Hugh; Shah, Khalid

doi:10.1016/s1470-2045(15)00039-x

Cited by 36 publications

(25 citation statements)

References 109 publications

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“…1, 2), are attractive therapies, but their clinical success rates have been limited (3). The targets of these drugs are usually peptides of cell transmembrane proteins; however, it is important to note that cell surfaces are covered by a glycan layer that is referred to as the glycocalyx (4).…”

Section: Introductionmentioning

confidence: 99%

A Novel Therapeutic Strategy for Pancreatic Cancer: Targeting Cell Surface Glycan Using rBC2LC-N Lectin–Drug Conjugate (LDC)

Shimomura

Oda

Tateno

et al. 2018

Molecular Cancer Therapeutics

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Various cancers, including pancreatic ductal adenocarcinoma (PDAC), remain intractable even with costly tumor-targeting antibody drugs. Because the outermost coatings of cancer cells are composed of cell-specific glycan layers (glycocalyx), lectins, proteins with glycan-binding potential, were evaluated for possible use as drug carriers in PDAC treatment. A human PDAC cell line with well-to-moderately differentiated properties (Capan-1) was subjected to lectin microarray analysis to identify specific lectin-glycan pairs. The selected lectin was fused with a bacterial exotoxin for the construction of a lectin-drug conjugate (LDC), and its safety and antitumor effects were evaluated. A specific affinity between a recombinant bacterial C-type lectin (rBC2LC-N) and Capan-1 was identified, and its positivity was confirmed in 69 human samples. In contrast to the belief that all lectins mediate harmful hemagglutination, rBC2LC-N did not cause hemagglutination with human erythrocytes and was safely administered to mice. The 50% inhibitory concentration of LDC to Capan-1 (1.04 pg/mL ¼ 0.0195 pmol/L) was 1/1,000 lower than that reported for conventional immunotoxins. The intraperitoneal administration of LDC reduced the tumor weight from 390 to 130.8 mg (P < 0.01) in an orthotopic model and reduced the number of nodules from 48 to 3 (P < 0.001) and improved survival from 62 to 105 days in a peritoneal dissemination model (P < 0.0001). In addition, the effect of LDC was reproduced in nodules from patient-derived PDAC xenografts through intravenous injection. Herein, we show the concept of utilizing lectins as drug carriers to target glycans on the cancer cell surface, highlighting new insights into cancer treatments.

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Section: Introductionmentioning

confidence: 99%

A Novel Therapeutic Strategy for Pancreatic Cancer: Targeting Cell Surface Glycan Using rBC2LC-N Lectin–Drug Conjugate (LDC)

Shimomura

Oda

Tateno

et al. 2018

Molecular Cancer Therapeutics

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“…On the other hand, similar to pertuzumab and trastuzumab, DM1 induces ADCC . Moreover, conjugated mAb with drugs, toxins or radioactive particles eliminate tumour cells directly …”

Section: Anit‐her2 Mabs and Derivativesmentioning

confidence: 99%

Monoclonal antibody-based therapeutics, targeting the epidermal growth factor receptor family: from herceptin to Pan HER

Moradi‐Kalbolandi

Hosseinzade

Salehi

et al. 2018

Journal of Pharmacy and Pharmacology

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Objectives Monoclonal antibody-based of cancer therapy has been considered as one of the most successful therapeutic strategies for both haematologic malignancies and solid tumours in the last two decades. Epidermal growth factor receptor (EGFR) family signalling pathways play a key role in the regulation of cell proliferation, survival and differentiation. Hence, anti-EGFR family mAbs is one of the most promising approaches in cancer therapy. Key findings Here, recent advances in anti-EGFR mAb including approved or successfully tested in preclinical and clinical studies have been reviewed. Although we focus on monoclonal antibodies against the EGF receptor, but the mechanisms underlying the effects of EGFR-specific mAb in cancer therapy, to some extend the resistance to existing anti-EGFR therapies and some therapeutic strategies to overcome resistance such as combination of mAbs on different pathways are briefly discussed as well. Summary The EGFR family receptors, is considered as an attractive target for mAb development to inhibit their consecutive activities in tumour growth and resistance. However, due to resistance mechanisms, the combination therapies may become a good candidate for targeting EGFR family receptors.

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“…While the drug release rate was modulated by altering the lipid composition, an in vitro study confirmed the TPP mitochondria targeting efficacy of TPP–CER–DOX based on quantitative analysis of the mitochondrial transmembrane potential reduction 65. Over the past decade, monoclonal antibodies targeting specific cell–surface antigens that were overexpressed in different tumor types have been substantially exploited for targeting cancer therapy 66. Leung et al developed anti‐epidermal growth factor receptors monoclonal antibodies (anti‐EGFR mAbs) functionalized with liposomal hybrid cerasomes, which target EGFR on cell surfaces 67.…”

Section: Bihlas For Targeting Deliverymentioning

confidence: 99%

Advancing the Pharmaceutical Potential of Bioinorganic Hybrid Lipid‐Based Assemblies

Wang

et al. 2018

Advanced Science

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Bioinspired lipid assemblies that mimic the elaborate architecture of natural membranes have fascinated researchers for a long time. These lipid assemblies have gone from being just an imperative platform for biophysical research to a pharmaceutical delivery system for biomedical applications. Despite success, these organized nanosystems are often subject to the mechanical instability and limited theranostic capability without adding any inconvenient modifications. To reach their advanced pharmaceutical potential, various bioinorganic hybrid lipid‐based assembles, which provide new opportunities to synergistically complement and improve therapeutic/diagnostic potential of existing lipid‐based nanomedicine with distinct mechanisms containing inorganic embedded surfactants, have recently been developed.

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Multifunctional receptor-targeting antibodies for cancer therapy

Cited by 36 publications

References 109 publications

A Novel Therapeutic Strategy for Pancreatic Cancer: Targeting Cell Surface Glycan Using rBC2LC-N Lectin–Drug Conjugate (LDC)

A Novel Therapeutic Strategy for Pancreatic Cancer: Targeting Cell Surface Glycan Using rBC2LC-N Lectin–Drug Conjugate (LDC)

Monoclonal antibody-based therapeutics, targeting the epidermal growth factor receptor family: from herceptin to Pan HER

Advancing the Pharmaceutical Potential of Bioinorganic Hybrid Lipid‐Based Assemblies

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