scholarly journals Single-Domain Antibodies as Therapeutic and Imaging Agents for the Treatment of CNS Diseases

Antibodies ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 27 ◽  
Author(s):  
Kasandra Bélanger ◽  
Umar Iqbal ◽  
Jamshid Tanha ◽  
Roger MacKenzie ◽  
Maria Moreno ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Building Blocks ◽  
Structural Features ◽  
Antibody Fragments ◽  
Single Domain ◽  
Imaging Agents ◽  
Cns Diseases ◽  
Single Domain Antibodies ◽  
Potential Therapeutics ◽  
Brain Barriers

Antibodies have become one of the most successful therapeutics for a number of oncology and inflammatory diseases. So far, central nervous system (CNS) indications have missed out on the antibody revolution, while they remain ‘hidden’ behind several hard to breach barriers. Among the various antibody modalities, single-domain antibodies (sdAbs) may hold the ‘key’ to unlocking the access of antibody therapies to CNS diseases. The unique structural features of sdAbs make them the smallest monomeric antibody fragments suitable for molecular targeting. These features are of particular importance when developing antibodies as modular building blocks for engineering CNS-targeting therapeutics and imaging agents. In this review, we first introduce the characteristic properties of sdAbs compared to traditional antibodies. We then present recent advances in the development of sdAbs as potential therapeutics across brain barriers, including their use for the delivery of biologics across the blood–brain and blood–cerebrospinal fluid (CSF) barriers, treatment of neurodegenerative diseases and molecular imaging of brain targets.

scholarly journals Single-Domain Antibodies for Targeting, Detection, and In Vivo Imaging of Human CD4+ Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Bjoern Traenkle ◽  
Philipp D. Kaiser ◽  
Stefania Pezzana ◽  
Jennifer Richardson ◽  
Marius Gramlich ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Cell ◽  
Inflammatory Diseases ◽  
Xenograft Model ◽  
Single Domain ◽  
Positron Emission ◽  
Depth Analysis ◽  
Single Domain Antibodies

The advancement of new immunotherapies necessitates appropriate probes to monitor the presence and distribution of distinct immune cell populations. Considering the key role of CD4+ cells in regulating immunological processes, we generated novel single-domain antibodies [nanobodies (Nbs)] that specifically recognize human CD4. After in-depth analysis of their binding properties, recognized epitopes, and effects on T-cell proliferation, activation, and cytokine release, we selected CD4-specific Nbs that did not interfere with crucial T-cell processes in vitro and converted them into immune tracers for noninvasive molecular imaging. By optical imaging, we demonstrated the ability of a high-affinity CD4-Nb to specifically visualize CD4+ cells in vivo using a xenograft model. Furthermore, quantitative high-resolution immune positron emission tomography (immunoPET)/MR of a human CD4 knock-in mouse model showed rapid accumulation of 64Cu-radiolabeled CD4-Nb1 in CD4+ T cell-rich tissues. We propose that the CD4-Nbs presented here could serve as versatile probes for stratifying patients and monitoring individual immune responses during personalized immunotherapy in both cancer and inflammatory diseases.

scholarly journals Multimeric single-domain antibody complexes protect against bunyavirus infections

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Paul J Wichgers Schreur ◽  
Sandra van de Water ◽  
Michiel Harmsen ◽  
Erick Bermúdez-Méndez ◽  
Dubravka Drabek ◽  
...  
Keyword(s):  
Rift Valley Fever Virus ◽  
Building Blocks ◽  
Single Domain ◽  
World Health ◽  
Great Promise ◽  
Single Domain Antibody ◽  
Valley Fever ◽  
Antiviral Therapies ◽  
Single Domain Antibodies ◽  
Health Organization

The World Health Organization has included three bunyaviruses posing an increasing threat to human health on the Blueprint list of viruses likely to cause major epidemics and for which no, or insufficient countermeasures exist. Here, we describe a broadly applicable strategy, based on llama-derived single-domain antibodies (VHHs), for the development of bunyavirus biotherapeutics. The method was validated using the zoonotic Rift Valley fever virus (RVFV) and Schmallenberg virus (SBV), an emerging pathogen of ruminants, as model pathogens. VHH building blocks were assembled into highly potent neutralizing complexes using bacterial superglue technology. The multimeric complexes were shown to reduce and prevent virus-induced morbidity and mortality in mice upon prophylactic administration. Bispecific molecules engineered to present two different VHHs fused to an Fc domain were further shown to be effective upon therapeutic administration. The presented VHH-based technology holds great promise for the development of bunyavirus antiviral therapies.

scholarly journals Camelid Single-Domain Antibodies (VHHs) against Crotoxin: A Basis for Developing Modular Building Blocks for the Enhancement of Treatment or Diagnosis of Crotalic Envenoming

Toxins ◽  
2018 ◽  
Vol 10 (4) ◽  
pp. 142 ◽  
Author(s):  
Marcos Luiz ◽  
Soraya Pereira ◽  
Nidiane Prado ◽  
Naan Gonçalves ◽  
Anderson Kayano ◽  
...  
Keyword(s):  
Building Blocks ◽  
Single Domain ◽  
Single Domain Antibodies

scholarly journals Single-domain antibodies for targeting, detection and in vivo imaging of human CD4+ cells

2021 ◽  
Author(s):  
Bjoern Traenkle ◽  
Philipp D. Kaiser ◽  
Stefania Pezzana ◽  
Jennifer Richardson ◽  
Marius Gramlich ◽  
...  
Keyword(s):  
In Vivo Imaging ◽  
Immune Cell ◽  
Inflammatory Diseases ◽  
Xenograft Model ◽  
Single Domain ◽  
High Signal ◽  
Cd4 Cells ◽  
Single Domain Antibodies

The advancement of new immunotherapies for the treatment of cancers, infections, immune-mediated inflammatory diseases, and autoimmune diseases necessitates the co-development of appropriate probes to detect and monitor the distribution and infiltration of distinct immune cell populations. Considering the key role of CD4+ T cells in regulating immunological processes, we have developed a set of novel single-domain antibodies (nanobodies, Nbs) that specifically recognize the human CD4 co-receptor in its native state on various CD4+ cells. Following detailed characterization of binding properties, epitope mapping, and site-directed functionalization, we selected biologically inert Nbs that do not affect T cell proliferation or cytokine expression in vitro. We used fluorescently labeled Nbs to track the presence and location of CD4+ cells in a xenograft model, demonstrating a high signal-to-background ratio by in vivo optical imaging. In summary, this study reports for the first time the generation and application of human CD4-specific Nbs for the detection and in vivo imaging of CD4+ cells in a preclinical animal model. We anticipate that the Nbs presented in this study will be versatile probes, e.g. in immunoPET imaging for patient stratification and for monitoring individual immune responses during personalized immunotherapy.

Camel Single-Domain Antibodies as Modular Building Blocks to Make Bivalent Constructs for Use in Immunotherapy of Cancer

2005 ◽  
pp. 493-495
Author(s):  
Virna Cortez-Retamozo ◽  
N. Backmann ◽  
P. Senter ◽  
U. Wernery ◽  
P. De Baetselier ◽  
...  
Keyword(s):  
Building Blocks ◽  
Single Domain ◽  
Immunotherapy Of Cancer ◽  
Single Domain Antibodies

scholarly journals Selection of Human Single Domain Antibodies (sdAb) Against Thymidine Kinase 1 and Their Incorporation Into sdAb-Fc Antibody Constructs For Potential Use In Cancer Therapy.

2021 ◽  
Author(s):  
Edwin J Velazquez ◽  
Jordan D Cress ◽  
Tyler B Humpherys ◽  
Toni O Mortimer ◽  
David M Bellini ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Thymidine Kinase ◽  
Limit Of Detection ◽  
Antibody Fragments ◽  
Single Domain ◽  
Mrna Levels ◽  
Thymidine Kinase 1 ◽  
Tumor Target ◽  
Phage Elisa ◽  
Single Domain Antibodies

Thymidine Kinase 1 (TK1) is primarily known as a cancer biomarker with good prognostic capabilities for liquid and solid malignancies. However, recent studies targeting TK1 at protein and mRNA levels have shown that TK1 may be useful as a tumor target. In order to examine the use of TK1 as a tumor target, it is necessary to develop therapeutics specific for TK1. Single domain antibodies (sdAbs), represent an exciting approach for the development of immunotherapeutics due to their cost-effective production and higher tumor penetration than conventional antibodies. In this study, we isolated sdAb fragments specific to human TK1 from a human sdAb library. A total of 400 sdAbs were screened through 5 rounds of selection by monoclonal phage ELISA. The most sensitive sdAb fragments were selected as candidates for preclinical testing. The sdAb fragments showed specificity for human TK1 in phage ELISA, Western blot analysis and had a limit of detection of 3.9 ng/ml for 4-H-TK1_A1 and 1.9 ng/ml for 4-H-TK1_D1. The antibody fragments were successfully expressed and used for detection of membrane associated TK1 (mTK1) through flow cytometry on cancer cells [lung (~95%), colon (~87%), breast (~53%)] and healthy human mono nuclear cells (MNC). The most sensitive antibody fragments, 4-H-TK1_A1 and 4-H-TK1_D1 were fused to an engineered IgG1 Fc fragment. When added to cancer cells expressing mTK1 co-cultured with human MNC, the anti-TK1-sdAb-IgG1_A1 and D1 were able to elicit a significant antibody-dependent cell-mediated cytotoxicity (ADCC) response by human MNCs against lung cancer cells compared to isotype controls (P<0.0267 and P<0.0265, respectively). To our knowledge this is the first time that the isolation and evaluation of human anti TK1 single domain antibodies using phage display technology has been reported. The antibody fragments isolated here may represent a valuable resource for the detection and the targeting of TK1 in tumor cells

Camelid and shark single domain antibodies: structural features and therapeutic potential

2017 ◽  
Vol 45 ◽  
pp. 10-16 ◽  
Author(s):  
Doreen Könning ◽  
Stefan Zielonka ◽  
Julius Grzeschik ◽  
Martin Empting ◽  
Bernhard Valldorf ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Structural Features ◽  
Single Domain ◽  
Single Domain Antibodies
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