Driving CARs with alternative navigation tools – the potential of engineered binding scaffolds

Zajc, Charlotte U.; Salzer, Benjamin; Taft, Joseph M.; Lehner, Manfred; Traxlmayr, Michael W.

doi:10.1111/febs.15523

Cited by 26 publications

(11 citation statements)

References 109 publications

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“…Similar to cytotoxicity tests, immunogenicity analysis data in the literature are not often encountered. Such tests were performed only in the aforementioned studies regarding vaccines [ 82 ] and chimeric T-cells [ 83 ], where immunogenic activation was desired. However, few—if any—scFvs used for other purposes have been tested in this fashion.…”

Section: Resultsmentioning

confidence: 99%

Dopamine D2 and Serotonin 5-HT1A Dimeric Receptor-Binding Monomeric Antibody scFv as a Potential Ligand for Carrying Drugs Targeting Selected Areas of the Brain

et al. 2022

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Targeted therapy uses multiple ways of ensuring that the drug will be delivered to the desired site. One of these ways is an encapsulation of the drug and functionalization of the surface. Among the many molecules that can perform such a task, the present work focused on the antibodies of single-chain variable fragments (scFvs format). We studied scFv, which specifically recognizes the dopamine D2 and serotonin 5-HT1A receptor heteromers. The scFvD2–5-HT1A protein was analyzed biochemically and biologically, and the obtained results indicated that the antibody is properly folded and non-toxic and can be described as low-immunogenic. It is not only able to bind to the D2–5-HT1A receptor heteromer, but it also influences the cAMP signaling pathway and—when surfaced on nanogold particles—it can cross the blood–brain barrier in in vitro models. When administered to mice, it decreased locomotor activity, matching the effect induced by clozapine. Thus, we are strongly convinced that scFvD2–5-HT1A, which was a subject of the present investigation, is a promising targeting ligand with the potential for the functionalization of nanocarriers targeting selected areas of the brain.

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Section: Resultsmentioning

confidence: 99%

Dopamine D2 and Serotonin 5-HT1A Dimeric Receptor-Binding Monomeric Antibody scFv as a Potential Ligand for Carrying Drugs Targeting Selected Areas of the Brain

et al. 2022

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“…Another beneficial feature of our platform is that the recognition element (Nb 6E ) can be linked to biological targets of choice through genetic fusion. The use of Nbs in place of conventional single-chain fragment variable (ScFv)-fusions can mitigate common issues such as construct aggregation and heavy chain–light chain domain mispairing …”

Section: Discussionmentioning

confidence: 99%

Rapid Covalent Labeling of Membrane Proteins on Living Cells Using a Nanobody–Epitope Tag Pair

2022

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Synthetic molecules that form a covalent bond upon binding to a targeted biomolecule (proximity-induced reactivity) are the subject of intense biomedical interest for the unique pharmacological properties imparted by irreversible binding. However, off-target covalent labeling and the lack of molecules with sufficient specificity limit more widespread applications. We describe the first example of a cross-linking platform that uses a synthetic peptide epitope and a single domain antibody (or nanobody) pair to form a covalent linkage rapidly and specifically. The rate of the cross-linking reaction between peptide and nanobody is faster than most other biocompatible cross-linking reactions, and it can be used to label live cells expressing receptor–nanobody fusions. The rapid kinetics of this system allowed us to probe the consequences on signaling for ligand cross-linking to the A2A-adenosine receptor. Our method may be generally useful to site-specifically link synthetic molecules to receptors on mammalian cell surfaces.

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Section: Discussionmentioning

confidence: 99%

Rapid covalent labeling of a GPCR on living cells using a nanobody-epitope tag pair to interrogate receptor pharmacology

Cabalteja

Cheloha

2022

Preprint

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Synthetic molecules that form a covalent bond upon binding to a targeted biomolecule (proximity-induced reactivity) are the subject of intense biomedical interest for the unique pharmacological properties imparted by irreversible binding. However, off-target covalent labeling and the lack of molecules with sufficient specificity limit more widespread applications. We describe the first example of a crosslinking platform that uses a synthetic peptide epitope and a single domain antibody (or nanobody) pair to form a covalent linkage rapidly and specifically. The rate of the crosslinking reaction between peptide and nanobody is faster than most other biocompatible crosslinking reactions, and it can be used to label live cells expressing receptor-nanobody fusions. The rapid kinetics of this system allowed us to probe the consequences on signaling for ligand crosslinking to the A2A-adenosine receptor. Our method may be generally useful to site-specifically link synthetic molecules to receptors on mammalian cell surfaces.

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Driving CARs with alternative navigation tools – the potential of engineered binding scaffolds

Cited by 26 publications

References 109 publications

Dopamine D2 and Serotonin 5-HT1A Dimeric Receptor-Binding Monomeric Antibody scFv as a Potential Ligand for Carrying Drugs Targeting Selected Areas of the Brain

Dopamine D2 and Serotonin 5-HT1A Dimeric Receptor-Binding Monomeric Antibody scFv as a Potential Ligand for Carrying Drugs Targeting Selected Areas of the Brain

Rapid Covalent Labeling of Membrane Proteins on Living Cells Using a Nanobody–Epitope Tag Pair

Rapid covalent labeling of a GPCR on living cells using a nanobody-epitope tag pair to interrogate receptor pharmacology

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