Antibodies and Derivatives Targeting DR4 and DR5 for Cancer Therapy

Dubuisson, Agathe; Micheau, Olivier

doi:10.3390/antib6040016

Cited by 61 publications

(56 citation statements)

References 225 publications

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“…For instance, when anti-trail-receptor IgG did not elicit a strong response, the switch to an IgM format resulted in stronger induction of trail-receptor-induced apoptosis [364]. Antibody formats that promote crosslinking are being assessed in clinical trials [365]. Likewise, other hinge and isotype formats also affect binding to targets [366].…”

Section: Avidity Modulationmentioning

confidence: 99%

Antibody Structure and Function: The Basis for Engineering Therapeutics

et al. 2019

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Antibodies and antibody-derived macromolecules have established themselves as the mainstay in protein-based therapeutic molecules (biologics). Our knowledge of the structure–function relationships of antibodies provides a platform for protein engineering that has been exploited to generate a wide range of biologics for a host of therapeutic indications. In this review, our basic understanding of the antibody structure is described along with how that knowledge has leveraged the engineering of antibody and antibody-related therapeutics having the appropriate antigen affinity, effector function, and biophysical properties. The platforms examined include the development of antibodies, antibody fragments, bispecific antibody, and antibody fusion products, whose efficacy and manufacturability can be improved via humanization, affinity modulation, and stability enhancement. We also review the design and selection of binding arms, and avidity modulation. Different strategies of preparing bispecific and multispecific molecules for an array of therapeutic applications are included.

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Section: Avidity Modulationmentioning

confidence: 99%

Antibody Structure and Function: The Basis for Engineering Therapeutics

et al. 2019

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“…The loss of Zn ion can lead to instability and loss of activity of human recombinant TRAIL (hrTRAIL) [27,28]. Several successful approaches have been utilized to overcome these challenges and to improve the cancer targeting potential of hrTRAIL that have been reviewed extensively elsewhere [3,29]. [30] using the Phyre2 server [32].…”

Section: Trail and Its Receptorsmentioning

confidence: 99%

“…In addition, because TRAIL provides an external trigger for apoptosis, it has the potential to overcome resistance to internal triggers of apoptosis after radiation or chemotherapy. There have been many excellent reviews on TRAIL biology and the mechanism of action with implication for therapeutic applications in recent years [2][3][4][5][6][7][8]. Here, we focus on the structure-function of TRAIL and extend our discussion to other members of the TNFSF/TNFRSF to illustrate the mechanism of signaling by reviewing the most up-to-date and relevant information from the scientific literature.…”

Section: Introductionmentioning

confidence: 99%

On the TRAIL of Better Therapies: Understanding TNFRSF Structure-Function

Vanamee

Faustman

2020

Cells

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Tumor necrosis factor (TNF) superfamily ligands show diverse biological functions, such as the induction of apoptotic cell death or cell survival and proliferation, making them excellent therapeutic targets for cancer and autoimmunity. We review the latest literature on TNF receptor superfamily signaling with a focus on structure-function. Using combinatorics, we argue that receptors that cluster on the cell surface and are activated by membrane-bound ligands need to arrange in a highly ordered manner, as the probability of random ligand and receptor arrangements matching up for receptor activation is very low. A growing body of evidence indicates that antiparallel receptor dimers that sequester the ligand binding site cluster on the cell surface, forming a hexagonal lattice. Upon ligand binding, this arrangement puts the activated receptors at the right distance to accommodate the downstream signaling partners. The data also suggest that the same geometry is utilized regardless of receptor type. The unified model provides important clues about TNF receptor signaling and should aid the design of better therapies for cancer and various immune mediated diseases.

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“…However, the application of these agents have been associated with some problems such as unfavourable side effects in normal cells and stimulation of immune response. Therefore, novel strategies are required to target TRAIL receptors [2]. Recently, TRAIL gene transfer offers the potential to improve stability, prolong half-life in plasma, specifically deliver to target sites and overcome TRAIL resistance.…”

Section: Introductionmentioning

confidence: 99%

Modified PAMAM vehicles for effective TRAIL gene delivery to colon adenocarcinoma:in vitroandin vivoevaluation

Pishavar

Attaranzadeh

Alibolandi

et al. 2018

Artificial Cells, Nanomedicine, and Biotechnology

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TRAIL (tumour necrosis factor-related apoptosis-inducing ligand) gene therapy is considered as one of the promising approaches for cancer treatment. Polyamidoamine (PAMAM) is one of the most extensively applied polymeric vector in gene delivery. In the current study, PAMAM (G4 and G5) dendrimers were modified with alkyl-carboxylate chain, PEG and cholesteryl chloroformate in order to enhance transfection efficiency through overcoming extracellular and intracellular barriers while reducing PAMAM cytotoxicity. Gene delivery efficiency of synthetized vectors was evaluated by both GFP (green fluorescent protein) reporter gene and TRAIL plasmid in colon cancer cells, in vitro and in vivo. The obtained results demonstrated that PAMAM G4-alkyl-PEG (3%)-Chol (5%)-TRAIL complexes at C/P ratio 4 could significantly increase cell death (29.45%) in comparison with unmodified PAMAM vector (15.5%). Moreover, in vivo study in C26 tumor-bearing BALB/c mice suggested that the prepared non-toxic safe vector could inhibit the tumor growth. This study represented the potent vehicle based on cholesterol-grafted PAMAM dendrimers with alkyl-PEG modification for efficient gene delivery in vitro and in vivo.

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Antibodies and Derivatives Targeting DR4 and DR5 for Cancer Therapy

Cited by 61 publications

References 225 publications

Antibody Structure and Function: The Basis for Engineering Therapeutics

Antibody Structure and Function: The Basis for Engineering Therapeutics

On the TRAIL of Better Therapies: Understanding TNFRSF Structure-Function

Modified PAMAM vehicles for effective TRAIL gene delivery to colon adenocarcinoma:in vitroandin vivoevaluation

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