On the humanization of VHHs: Prospective case studies, experimental and computational characterization of structural determinants for functionality DOI Creative Commons
Monica L. Fernández‐Quintero, Enrico Guarnera, Djordje Müsil

и другие.

Protein Science, Год журнала: 2024, Номер 33(11)

Опубликована: Окт. 18, 2024

The humanization of camelid-derived variable domain heavy chain antibodies (VHHs) poses challenges including immunogenicity, stability, and potential reduction affinity. Critical to this process are complementarity-determining regions (CDRs), Vernier Hallmark residues, shaping the three-dimensional fold influencing VHH structure function. Additionally, presence non-canonical disulfide bonds further contributes conformational stability antigen binding. In study, we systematically humanized two VHHs targeting natural cytotoxicity receptor NKp30. Key structural positions in were exchanged with residues from most similar human germline sequences. resulting variants characterized for binding affinities, yield, purity. Structural modes elucidated through crystal determination AlphaFold2 predictions, providing insights into differences Comparative molecular dynamics characterizations selected performed rationalize their functional properties elucidate role specific sequence motifs Furthermore, systematic analyses next-generation sequencing (NGS) Protein Data Bank (PDB) data was conducted, shedding light on significance general. Overall, study provides valuable determinants governing VHHs, offering a roadmap rational design, humanization, optimization therapeutic applications.

Язык: Английский

NANOBODIES®: A Review of Diagnostic and Therapeutic Applications DOI Open Access
Bo-kyung Jin, Steven Odongo, Magdalena Radwanska

и другие.

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(6), С. 5994 - 5994

Опубликована: Март 22, 2023

NANOBODY® (a registered trademark of Ablynx N.V) molecules (Nbs), also referred to as single domain-based VHHs, are antibody fragments derived from heavy-chain only IgG antibodies found in the

Язык: Английский

Процитировано

184
Past, Present and (Foreseeable) Future of Biological Anti-TNF Alpha Therapy DOI Open Access
Gian Marco Leone, Katia Mangano, Maria Cristina Petralia

и другие.

Journal of Clinical Medicine, Год журнала: 2023, Номер 12(4), С. 1630 - 1630

Опубликована: Фев. 17, 2023

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

Язык: Английский

Процитировано

89
The Dawn of a New Era: Targeting the “Undruggables” with Antibody-Based Therapeutics DOI
Linghui Qian,

Xuefen Lin,

Xue Gao

и другие.

Chemical Reviews, Год журнала: 2023, Номер 123(12), С. 7782 - 7853

Опубликована: Май 15, 2023

The high selectivity and affinity of antibodies toward their antigens have made them a highly valuable tool in disease therapy, diagnosis, basic research. A plethora chemical genetic approaches been devised to make accessible more "undruggable" targets equipped with new functions illustrating or regulating biological processes precisely. In this Review, addition introducing how naked various antibody conjugates (such as antibody-drug conjugates, antibody-oligonucleotide antibody-enzyme etc.) work therapeutic applications, special attention has paid chemistry tools helped optimize the outcome (i.e., enhanced efficacy reduced side effects) facilitate multifunctionalization antibodies, focus on emerging fields such targeted protein degradation, real-time live-cell imaging, catalytic labeling decaging spatiotemporal control well engagement inside cells. With advances modern biotechnology, well-designed derivatives via size miniaturization together efficient delivery systems emerged, which gradually improved our understanding important paved way pursue novel for potential treatments diseases.

Язык: Английский

Процитировано

71
TROP2-directed nanobody-drug conjugate elicited potent antitumor effect in pancreatic cancer DOI Creative Commons

Caili Xu,

Min Zhu, Qian Wang

и другие.

Journal of Nanobiotechnology, Год журнала: 2023, Номер 21(1)

Опубликована: Ноя. 6, 2023

Pancreatic cancer is a highly aggressive malignancy with limited treatment options and poor prognosis. Trophoblast cell surface antigen 2 (TROP2), overexpressed in the tumors of more than half pancreatic patients, has been identified as potential target for antibody-drug conjugates (ADCs). Almost all reported TROP2-targeted ADCs are IgG type have poorly studied cancer. Here, we aimed to develop novel nanobody-drug conjugate (NDC) targeting TROP2 cancer.In this study, developed NDC, HuNbTROP2-HSA-MMAE, TROP2-positive HuNbTROP2-HSA-MMAE characterized by use nanobodies against human serum albumin (HSA) drug-antibody ratio 1. exhibited specific binding was internalized into tumor cells high endocytosis efficiency within 5 h, followed intracellular translocation lysosomes release MMAE induce apoptosis through caspase-3/9 pathway. In xenograft model cancer, doses 0.2 mg/kg 1 demonstrated significant antitumor effects, dose even eradicated tumor.HuNbTROP2-HSA-MMAE desirable affinity, internalization activity. It holds promise therapeutic option

Язык: Английский

Процитировано

53
A pivotal decade for bispecific antibodies? DOI Creative Commons
Marlena Surowka, Christian Klein

mAbs, Год журнала: 2024, Номер 16(1)

Опубликована: Март 11, 2024

Bispecific antibodies (bsAbs) are a class of that can mediate novel mechanisms action compared to monospecific monoclonal (mAbs). Since the discovery mAbs and their adoption as therapeutic agents in 1980s 1990s, development bsAbs has held substantial appeal. Nevertheless, only three (catumaxomab, blinatumomab, emicizumab) were approved through end 2020. However, since then, 11 received regulatory agency approvals, which nine (amivantamab, tebentafusp, mosunetuzumab, cadonilimab, teclistamab, glofitamab, epcoritamab, talquetamab, elranatamab) for treatment cancer two (faricimab, ozoralizumab) non-oncology indications. Notably, 13 currently bsAbs, two, emicizumab faricimab, have achieved blockbuster status, showing promise this therapeutics. In 2020s, approval additional be expected hematological malignancies, solid tumors indications, establishing essential part armamentarium.

Язык: Английский

Процитировано

23
Discovery of nanobodies: a comprehensive review of their applications and potential over the past five years DOI Creative Commons

Elena Alexander,

Kam W. Leong

Journal of Nanobiotechnology, Год журнала: 2024, Номер 22(1)

Опубликована: Окт. 26, 2024

Nanobodies (Nbs) are antibody fragments derived from heavy-chain-only IgG antibodies found in the Camelidae family as well cartilaginous fish. Their unique structural and functional properties, such their small size, ability to be engineered for high antigen-binding affinity, stability under extreme conditions, ease of production, have made them promising tools diagnostics therapeutics. This potential was realized 2018 with approval caplacizumab, world's first Nb-based drug. Currently, Nbs being investigated clinical trials a broad range treatments, including targeted therapies against PDL1 Epidermal Growth Factor Receptor (EGFR), cardiovascular diseases, inflammatory neurodegenerative disorders Alzheimer's disease, Parkinson's amyotrophic lateral sclerosis. They also studied detecting imaging autoimmune conditions infectious diseases severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A variety methods now available generate target-specific quickly efficiently at low costs, increasing accessibility. article examines these diverse applications roles. Only most recent articles published last five years been used summarize advanced developments field.

Язык: Английский

Процитировано

17
Trends in nanobody radiotheranostics DOI
Xingbo Long,

Sixuan Cheng,

Xiaoli Lan

и другие.

European Journal of Nuclear Medicine and Molecular Imaging, Год журнала: 2025, Номер unknown

Опубликована: Янв. 13, 2025

Язык: Английский

Процитировано

2
Nanobodies targeting the tumor microenvironment and their formulation as nanomedicines DOI Creative Commons

Liudmyla Maksymova,

Yannick A. Pilger,

Lutz Nuhn

и другие.

Molecular Cancer, Год журнала: 2025, Номер 24(1)

Опубликована: Март 4, 2025

Among the emerging strategies for cancer theranostics, nanomedicines offer significant promise in advancing both patients' diagnosis and treatment. In combination with nanobodies, can potentially enhance precision efficiency of drug or imaging agent delivery, addressing key limitations current approaches, such as off-target toxicities. The development will be further accelerated by creation smart nanoparticles, their integration immunotherapy. Obviously, success nano-immunotherapy depend on a comprehensive understanding tumor microenvironment, including complex interplay mechanisms that drive cancer-mediated immunosuppression immune escape. Hence, effective therapeutic targeting microenvironment requires modulation cell function, overcoming resistance associated stromal components extracellular matrix, and/or direct elimination cells. Identifying molecules involved progression is, therefore, essential developing therapies diagnostic tools predict patient responses to treatment monitor outcomes. Current are being designed careful consideration factors choice carrier (e.g., biocompatibility, controlled cargo release) moiety. unique properties nanobodies make them an engineering tool target biological high affinity specificity. this review, we focus latest applications various purposes. We also explore main types nanoparticles used immunotherapies, well formulating nanoparticle-nanobody conjugates. Finally, highlight how nanobody-nanoparticle formulations nanomedicines.

Язык: Английский

Процитировано

2
Current status and future expectations of nanobodies in oncology trials DOI Creative Commons
Tessa De Pauw, Lynn De Mey, Jens Debacker

и другие.

Expert Opinion on Investigational Drugs, Год журнала: 2023, Номер 32(8), С. 705 - 721

Опубликована: Авг. 3, 2023

Introduction Monoclonal antibodies have revolutionized personalized medicine for cancer in recent decades. Despite their broad application oncology, large size and complexity may interfere with successful tumor targeting certain applications of diagnosis therapy. Nanobodies unique structural pharmacological features compared to monoclonal successfully been used as complementary anti-cancer diagnostic and/or therapeutic tools.Areas covered Here, an overview is given the nanobody-based diagnostics therapeutics that or are currently being tested oncological clinical trials. Furthermore, preclinical developments, which likely be translated into clinic near future, highlighted.Expert opinion Overall, presented studies show potential nanobodies field making it more will clinically approved upcoming future.

Язык: Английский

Процитировано

21
Single domain antibody: Development and application in biotechnology and biopharma DOI Creative Commons

Ting Yu,

Fang Zheng, Wenbo He

и другие.

Immunological Reviews, Год журнала: 2024, Номер unknown

Опубликована: Авг. 21, 2024

Summary Heavy‐chain antibodies (HCAbs) are a unique type of devoid light chains, and comprised two heavy chains‐only that recognize their cognate antigen by virtue single variable domain also referred to as VHH, antibody (sdAb), or nanobody (Nb). These functional HCAbs, serendipitous discovered about three decades ago, exclusively found in camelids, comprising dromedaries, camels, llamas, vicugnas. Nanobodies have become an essential tool biomedical research medicine, both diagnostics therapeutics due beneficial properties: small size, high stability, strong antigen‐binding affinity, low immunogenicity, production cost, straightforward engineering into more potent affinity reagents. The occurrence HCAbs camelids remains intriguing. It is believed be evolutionary adaptation, equipping with robust adaptive immune defense suitable respond the pressure from pathogenic invasion necessitating profound recognition neutralization. This innovation led simplified HCAb structure, possibly supported genetic mutations drift, allowing mutation diversification chain gene constant regions. Beyond understanding origins, application nanobodies has significantly advanced over past 30 years. Alongside expanding laboratory research, there been rapid increase patent for nanobodies. introduction commercial drugs such Cablivi, Nanozora, Envafolimab, Carvykti boosted confidence among potential. review explores history ontogeny, applications biotechnology pharmaceuticals, focusing on approved ongoing medical pipelines.

Язык: Английский

Процитировано

8