Camelid Single-Domain Antibodies: Promises and Challenges as Lifesaving Treatments

Arbabi‐Ghahroudi, Mehdi

doi:10.3390/ijms23095009

Cited by 46 publications

(45 citation statements)

References 179 publications

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“…Now, about 16 therapeutic nanobodies have entered clinical trials for various disease types ( 36 ). In 2019, Caplacizumab, a bivalent nanobody targeting von Willebrand, received approval from the FDA for the treatment of patients with thrombotic thrombocytopenic purpura ( 37 ).…”

Section: Nanobodies: the Smaller Variant Of Antibodiesmentioning

confidence: 99%

Nanobodies in cell-mediated immunotherapy: On the road to fight cancer

et al. 2023

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The immune system is essential in recognizing and eliminating tumor cells. The unique characteristics of the tumor microenvironment (TME), such as heterogeneity, reduced blood flow, hypoxia, and acidity, can reduce the efficacy of cell-mediated immunity. The primary goal of cancer immunotherapy is to modify the immune cells or the TME to enable the immune system to eliminate malignancies successfully. Nanobodies, known as single-domain antibodies, are light chain-free antibody fragments produced from Camelidae antibodies. The unique properties of nanobodies, including high stability, reduced immunogenicity, enhanced infiltration into the TME of solid tumors and facile genetic engineering have led to their promising application in cell-mediated immunotherapy. They can promote the cancer therapy either directly by bridging between tumor cells and immune cells and by targeting cancer cells using immune cell-bound nanobodies or indirectly by blocking the inhibitory ligands/receptors. The T-cell activation can be engaged through anti-CD3 and anti-4-1BB nanobodies in the bispecific (bispecific T-cell engagers (BiTEs)) and trispecific (trispecific T-cell engager (TriTEs)) manners. Also, nanobodies can be used as natural killer (NK) cell engagers (BiKEs, TriKEs, and TetraKEs) to create an immune synapse between the tumor and NK cells. Nanobodies can redirect immune cells to attack tumor cells through a chimeric antigen receptor (CAR) incorporating a nanobody against the target antigen. Various cancer antigens have been targeted by nanobody-based CAR-T and CAR-NK cells for treating both hematological and solid malignancies. They can also cause the continuation of immune surveillance against tumor cells by stopping inappropriate inhibition of immune checkpoints. Other roles of nanobodies in cell-mediated cancer immunotherapy include reprogramming macrophages to reduce metastasis and angiogenesis, as well as preventing the severe side effects occurring in cell-mediated immunotherapy. Here, we highlight the critical functions of various immune cells, including T cells, NK cells, and macrophages in the TME, and discuss newly developed immunotherapy methods based on the targeted manipulation of immune cells and TME with nanobodies.

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Section: Nanobodies: the Smaller Variant Of Antibodiesmentioning

confidence: 99%

Nanobodies in cell-mediated immunotherapy: On the road to fight cancer

et al. 2023

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“…Nanobodies are much smaller than human mAbs and are usually found in camelids like alpacas and llamas. They have been proposed as anti-tumor therapeutics [ 68 ] and have found recent application in anti-SARS-CoV-2 research projects [ 69 ]. Nanobodies have certain advantages compared to mAbs.…”

Section: Progress In Developing Antiviral Mabsmentioning

confidence: 99%

Recent Progress in the Discovery and Development of Monoclonal Antibodies against Viral Infections

et al. 2022

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Monoclonal antibodies (mAbs), the new revolutionary class of medications, are fast becoming tools against various diseases thanks to a unique structure and function that allow them to bind highly specific targets or receptors. These specialized proteins can be produced in large quantities via the hybridoma technique introduced in 1975 or by means of modern technologies. Additional methods have been developed to generate mAbs with new biological properties such as humanized, chimeric, or murine. The inclusion of mAbs in therapeutic regimens is a major medical advance and will hopefully lead to significant improvements in infectious disease management. Since the first therapeutic mAb, muromonab-CD3, was approved by the U.S. Food and Drug Administration (FDA) in 1986, the list of approved mAbs and their clinical indications and applications have been proliferating. New technologies have been developed to modify the structure of mAbs, thereby increasing efficacy and improving delivery routes. Gene delivery technologies, such as non-viral synthetic plasmid DNA and messenger RNA vectors (DMabs or mRNA-encoded mAbs), built to express tailored mAb genes, might help overcome some of the challenges of mAb therapy, including production restrictions, cold-chain storage, transportation requirements, and expensive manufacturing and distribution processes. This paper reviews some of the recent developments in mAb discovery against viral infections and illustrates how mAbs can help to combat viral diseases and outbreaks.

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“…Once isolated, a fusion of nanobodies may be generated, either by direct chemical bonding creating a 25 kDa bivalent structure or by binding to human Fc chain fragments, creating human-compatible 50 kDa structures. The bivalent nanobodies quickly proved to be very stable at high temperatures and able to bind to specific epitopes not easily accessible by conventional mAbs [ 26 ].…”

Section: Introduction: History Of Biologicsmentioning

confidence: 99%

Past, Present and (Foreseeable) Future of Biological Anti-TNF Alpha Therapy

Leone

Mangano

Petralia

et al. 2023

JCM

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Due to the key role of tumor necrosis factor-alpha (TNF-α) in the pathogenesis of immunoinflammatory diseases, TNF-α inhibitors have been successfully developed and used in the clinical treatment of autoimmune disorders. Currently, five anti-TNF-α drugs have been approved: infliximab, adalimumab, golimumab, certolizumab pegol and etanercept. Anti-TNF-α biosimilars are also available for clinical use. Here, we will review the historical development as well as the present and potential future applications of anti-TNF-α therapies, which have led to major improvements for patients with several autoimmune diseases, such as rheumatoid arthritis (RA), ankylosing spondylitis (AS), Crohn’s disease (CD), ulcerative colitis (UC), psoriasis (PS) and chronic endogenous uveitis. Other therapeutic areas are under evaluation, including viral infections, e.g., COVID-19, as well as chronic neuropsychiatric disorders and certain forms of cancer. The search for biomarkers able to predict responsiveness to anti-TNF-α drugs is also discussed.

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Camelid Single-Domain Antibodies: Promises and Challenges as Lifesaving Treatments

Cited by 46 publications

References 179 publications

Nanobodies in cell-mediated immunotherapy: On the road to fight cancer

Nanobodies in cell-mediated immunotherapy: On the road to fight cancer

Recent Progress in the Discovery and Development of Monoclonal Antibodies against Viral Infections

Past, Present and (Foreseeable) Future of Biological Anti-TNF Alpha Therapy

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