Review
Cell Biology
Jan Gettemans, Brian De Dobbelaer
Summary: Single-domain antibodies derived from camelids and sharks, known as nanobodies, have gained attention for their high specificity and affinity binding to targets. Their key features including single-domain nature, small size, affordable high-level expression, and flexibility in altering primary structure have made them appealing for researchers and valuable in biomedical research.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Wenyi Wang, Jumao Yuan, Changan Jiang
Summary: Nanobodies, variable domains of heavy chain-only antibodies isolated from camelids, exhibit unique features such as small size, high stability, and cryptic epitopes accessibility, making them ideal for advanced applications in plants and animals. Current applications of nanobodies in plant science and biotechnology include expression in plants, biotechnological applications, toxin and pathogen determination, and resistance against plant pathogens. Prospects and challenges of nanobody applications in plants are also discussed in this review.
PLANT MOLECULAR BIOLOGY
(2021)
Article
Oncology
Yan Yan, Xiao Cheng, Lin Li, Rumeng Zhang, Yong Zhu, Zhengsheng Wu, Keshuo Ding
Summary: The study successfully constructed HER2-nanobody and demonstrated its ability to inhibit growth and promote apoptosis of HER2-positive breast cancer cells. HER2-nanobody exerts its tumor suppressive role by inhibiting the phosphorylation of ERK and AKT.
FRONTIERS IN ONCOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Chaolemeng Bao, Quanli Gao, Lin-Lin Li, Lu Han, Bingxiang Zhang, Yijin Ding, Zongpei Song, Ruining Zhang, Jishuai Zhang, Xian-Hui Wu
Summary: The use of nanobodies as the antigen binding domain in CAR-T therapy has shown efficacy in targeting various tumor-specific antigens both in vitro and in vivo. Nanobody-modified CAR-T demonstrates comparable clinical effects to traditional CAR-T and presents great potential for addressing more challenging tasks.
Review
Biochemistry & Molecular Biology
Mehdi Arbabi-Ghahroudi
Summary: Since the discovery of camelid heavy-chain antibodies in 1993, there has been great interest in the research and application of nanobodies. After years of effort, the first nanobody drug was approved in 2018-2019 for the treatment of rare blood clotting disorders. Despite intellectual property restrictions, nanobodies have the potential to become mainstream biotherapeutics in the future.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Seisho Kinoshita, Makoto Nakakido, Chinatsu Mori, Daisuke Kuroda, Jose M. M. Caaveiro, Kouhei Tsumoto
Summary: Research on VHH engineering for biotechnological and clinical applications is actively conducted to take advantage of their favorable biophysical properties. Humanization of camelid VHHs through CDR grafting with a humanized VHH in clinical trials resulted in changes to the affinity, thermal stability, and conformational structure. Mutational and back-mutational analyses on the framework regions revealed the significant contribution of bulky residues and intramolecular interactions to the properties of VHHs. Back-mutations restored intramolecular interactions, resulting in increased thermal stability and affinity, showing the potential for designing VHHs by modifying the framework region without altering the CDRs.
Article
Biochemistry & Molecular Biology
Seisho Kinoshita, Makoto Nakakido, Chinatsu Mori, Daisuke Kuroda, Jose M. M. Caaveiro, Kouhei Tsumoto
Summary: Camelid single domain antibodies, known as VHHs or Nanobodies, are versatile tools for various biotechnological and clinical applications due to their favorable biophysical properties. Research on VHH engineering has shown that modifications can impact affinity and thermal stability, highlighting the importance of interactions between the framework region and CDR3 for regulating VHH characteristics.
Article
Radiology, Nuclear Medicine & Medical Imaging
Yutian Feng, Zhengyuan Zhou, Darryl McDougald, Rebecca L. Meshaw, Ganesan Vaidyanathan, Michael R. Zalutsky
Summary: The site-specific strategy utilizing a radioiodinated, residualizing maleimido moiety and the anti-HER2 sdAb showed promising results for tumor targeting with lower normal tissue uptake.
NUCLEAR MEDICINE AND BIOLOGY
(2021)
Article
Medicine, Research & Experimental
Henk van Faassen, Dong-Hyeon Jo, Shannon Ryan, Michael J. Lowden, Shalini Raphael, C. Roger MacKenzie, Seung-Hwan Lee, Greg Hussack, Kevin A. Henry
Summary: Novel llama single-domain antibodies against CD16 showed high affinity for human and cynomolgus monkey CD16, but not murine CD16. These antibodies may have applications in cancer immunotherapy.
MOLECULAR PHARMACEUTICS
(2021)
Article
Microbiology
Greg Hussack, Martin A. Rossotti, Henk van Faassen, Tomohiko Murase, Luiz Eugenio, Joseph D. Schrag, Kenneth K. -S. Ng, Jamshid Tanha
Summary: Crystal structures of camelid heavy-chain antibody variable domains (V(H)Hs) bound to fragments of the combined repetitive oligopeptides domain of Clostridiodes difficile toxin A (TcdA) revealed a spatial arrangement between VHH A20 and VHH A26. Based on this observation, a biparatopic fusion protein A20-A26 was generated, which showed improved binding affinity and neutralization potency compared to unfused A20 and A26 V(H)Hs. A20-A26 demonstrated higher potency than various control constructs. Size-exclusion chromatography-multiangle light scattering (SEC-MALS) analysis confirmed the 1:1 stoichiometry and simultaneous engagement of both A20 and A26 epitopes by A20-A26, in contrast to the varied and heterogeneous binding modes of control constructs. These results underscore the importance of molecular geometric constraints in generating highly potent antibody-based reagents.
FRONTIERS IN MICROBIOLOGY
(2023)
Article
Oncology
Elodie Duray, Margaux Lejeune, Frederic Baron, Yves Beguin, Nick Devoogdt, Ahmet Krasniqi, Yoline Lauwers, Yong Juan Zhao, Matthias D'Huyvetter, Mireille Dumoulin, Jo Caers
Summary: This study developed anti-CD38 single-domain antibodies (sdAbs) for tracing and targeted radionuclide therapy, with the lead sdAb 2F8 showing excellent affinity, stability, lack of competition with daratumumab, and low receptor-mediated internalisation. In vivo, radiolabelled 2F8 sdAb demonstrated specific and sustained tumour retention with high tumour-to-normal tissue ratios. Therapeutically, the Lu-177-labelled 2F8 sdAb induced dose-dependent tumour regression and prolonged survival in a myeloma xenograft model, highlighting the theranostic potential of radiolabelled anti-CD38 sdAbs for multiple myeloma monitoring and treatment.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Martin A. Rossotti, Kasandra Belanger, Kevin A. Henry, Jamshid Tanha
Summary: Single-domain antibodies have desirable properties as biologic drugs, but their sequences may increase immunogenicity risks. While most clinical trials show minimal immunogenicity, special caution is needed for highly potent sdAbs. Further research is needed to establish humanization thresholds to maximize human sequence content without compromising binding affinity or stability.
Article
Multidisciplinary Sciences
Jessica Hong, Hyung Joon Kwon, Raul Cachau, Catherine Z. Chen, Kevin John Butay, Zhijian Duan, Dan Li, Hua Ren, Tianyuzhou Liang, Jianghai Zhu, Venkata P. Dandey, Negin P. Martin, Dominic Esposito, Uriel Ortega-Rodriguez, Miao Xu, Mario J. Borgnia, Hang Xie, Mitchell Ho
Summary: The study constructed large dromedary camel VHH phage libraries and successfully isolated two high-affinity nanobodies that showed broad neutralization activity against SARS-CoV-2 and its variants. These nanobodies can be used for therapeutic purposes against COVID-19 variants, and the dromedary camel VHH phage libraries serve as a unique platform for rapidly isolating potent nanobodies against future emerging viruses.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Oncology
Yasaman Asaadi, Fatemeh Fazlollahi Jouneghani, Sara Janani, Fatemeh Rahbarizadeh
Summary: By comparing the structure and properties of camelid antibodies (VHHs) and single-chain variable fragments (scFvs), it can be determined which one is more suitable for their respective therapeutic, diagnostic, and research applications.
BIOMARKER RESEARCH
(2021)
Article
Medicine, Research & Experimental
Mahmoud Ganji, Pooria Safarzadeh Kozani, Fatemeh Rahbarizadeh
Summary: Monoclonal antibody-based immunotherapies have shown promising results in treating immunological and oncological conditions. CD19 is a qualified antigen for B-cell neoplasms treatment, and VHHs have advantages over conventional mAbs as potential therapeutics and diagnostic tools. By isolating CD19-specific VHHs from a novel immune library using phage display, it was demonstrated that selected VHHs exhibited high specificity, sensitivity, and affinity to CD19, making them potential targeting tools for CD19-based immunotherapeutics.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Article
Oncology
Jeanet F. Karchoud, Anja J. Th C. M. de Kruif, Femke Lamers, Myra E. van Linde, Joyce M. Van Dodewaard-de Jong, Annemarie M. J. Braamse, Mirjam A. G. Sprangers, Aartjan T. F. Beekman, Henk M. W. Verheul, Joost Dekker
Summary: This study explores the indicators and strategies used by oncologists and nurses to determine the need for professional mental health care in cancer patients. The findings suggest that oncologists and nurses consider multiple factors, including the patient's emotional well-being and specific indicators of emotional problems, when making the decision to refer patients for professional mental health care.
JOURNAL OF CANCER SURVIVORSHIP
(2023)
Article
Cell Biology
Matthieu R. Zeronian, Sofia Doulkeridou, Paul M. P. van Bergen en Henegouwen, Bert J. C. Janssen
Summary: This study presents the molecular mechanism of EgB4 nanobody binding to EGFR and its non-inhibitory role in EGFR signaling. The findings provide a basis for the application of EgB4 in therapy and the localization of EGFR-associated tumors.
BMC MOLECULAR AND CELL BIOLOGY
(2022)
Article
Surgery
J. K. de Bakker, L. L. Meijer, B. M. Zonderhuis, H. J. van der Vliet, F. Daams, N. C. T. van Grieken, B. Lissenberg-Witte, G. Kazemier
Summary: This study investigated the benefit of adjuvant chemotherapy for patients with resectable duodenal adenocarcinoma. The results showed no statistically significant survival benefit for adjuvant chemotherapy after curative resection in stages II and III patients. Future studies with specified treatment regimens and thorough stratification for prognostic factors are needed to determine the role of adjuvant therapy more definitively.
ACTA CHIRURGICA BELGICA
(2023)
Article
Immunology
Angelique Jarade, Zacarias Garcia, Solenne Marie, Abdi Demera, Immo Prinz, Philippe Bousso, James P. Di Santo, Nicolas Serafini
Summary: Serafini and colleagues find that intestinal villus ILC3s acquire migratory 'patrolling' attributes and enhanced cytokine expression in response to inflammation. These findings reveal notable differences between ILC3s and T cells in immunosurveillance, with ILC3s showing adaptation towards mucosal immunosurveillance after inflammation.
Meeting Abstract
Hematology
Sarah Lawless, Curly Morris, Dirk-Jan Eikema, Linda Kostner, Friedrich Stoelzel, Nicolaus Kroeger, Uwe Platzbecker, Wolfgang Bethge, Peter Brossart, Renato Fanin, Juergen Finke, Jurgen Kuball, Veronique Leblond, Emma Nicholson, Jakob Passweg, Daniele Avenoso, Jacques-Olivier Bay, Ali Bazarbachi, Dolores Caballero, Joanna Drozd-Sokolowska, Christof Scheid, Donal P. McLornan, Marie Robin, Ibrahim Yakoub-Agha
Article
Immunology
Eline van Diest, Mara J. T. Nicolasen, Lovro Kramer, Jiali Zheng, Patricia Hernandez-Lopez, Dennis X. Beringer, Jurgen Kuball
Summary: In this study, we developed a novel T cell engager concept called GAB by utilizing γδTCR as a tumor targeting domain. The γδ ECTO-alpha CD3-dimer design was found to be superior in function compared to monomers and does not induce T cell activation without simultaneous tumor engagement.
FRONTIERS IN IMMUNOLOGY
(2023)
Letter
Biophysics
Klaartje Nijssen, Kasper Westinga, Anniek Stuut, Anke Janssen, Anna van Rhenen, Lotte van der Wagen, Laura G. M. Daenen, Rimke Oostvogels, Moniek A. de Witte, Juergen Kuball
BONE MARROW TRANSPLANTATION
(2023)
Letter
Biophysics
Laura G. M. Daenen, Jan-Tom van der Bruggen, Roos J. Leguit, Lotte E. van der Wagen, Anna van Rhenen, Herman F. Wunderink, Moniek A. de Witte, Anke H. W. Bruns, Jurgen Kuball
BONE MARROW TRANSPLANTATION
(2023)
Letter
Biophysics
M. A. de Witte, J. E. Mooyaart, J. D. Hoogenboom, C. Chabannon, F. Malard, A. Ruggeri, J. Kuball
BONE MARROW TRANSPLANTATION
(2023)
Article
Biochemistry & Molecular Biology
Eline J. H. van Houtum, Esther D. Kers-Rebel, Maaike W. Looman, Erik Hooijberg, Christian Bull, Daniel Granado, Lenneke A. M. Cornelissen, Gosse J. Adema
Summary: Tumors create an immunosuppressive tumor microenvironment by altering protein expression and changing their glycosylation status, like altered expression of sialoglycans. Siglec-7, an inhibitory immune receptor similar to PD-1, is used by cancer cells as a glycoimmune checkpoint to evade the immune system. The exact cellular and molecular conditions required for Siglec-7-mediated immune cell inhibition remain largely unknown.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Oncology
Thomas Kimman, Anne Slomp, Anne Martens, Sarah Grabherr, Shuang Li, Eline van Diest, Jan Meeldijk, Jurgen Kuball, Monique C. Minnema, Eric Eldering, Niels Bovenschen, Zsolt Sebestyen, Victor Peperzak
Summary: Gene engineered CAR T cells have shown promising initial clinical responses in cancer patients; however, resistance mechanisms in cancer cells can limit the effectiveness of CAR T cell-mediated killing. Serpin B9 expression in cancer cells can lead to resistance towards CAR T cells, and inhibiting or bypassing serpin B9 may improve CAR T cell responses.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Oncology
Hanne Lefrere, Kat Moore, Giuseppe Floris, Joyce Sanders, Iris M. Seignette, Tycho Bismeijer, Dennis Peters, Annegien Broeks, Erik Hooijberg, Kristel Van Calsteren, Patrick Neven, Ellen Warner, Fedro Alessandro Peccatori, Sibylle Loibl, Charlotte Maggen, Sileny N. Han, Katarzyna J. Jerzak, Daniela Annibali, Diether Lambrechts, Karin E. de Visser, Lodewyk Wessels, Liesbeth Lenaerts, Frederic Amant
Summary: Patients with postweaning postpartum breast cancer (PP-BCPW) have a poor prognosis compared with other types of breast cancer. This study found that PP-BCPW patients with low expression of immunoglobulin genes but high infiltration of plasma B cells have an increased risk of metastasis and death.
CLINICAL CANCER RESEARCH
(2023)
Article
Oncology
Hielke M. de Vries, Tynisha S. Rafael, Alberto Gil-Jimenez, Jeantine M. de Feijter, Elise Bekers, Elsbeth van der Laan, Marta Lopez-Yurda, Erik Hooijberg, Annegien Broeks, Dennis Peters, Iris M. Seignette, Floris J. Pos, Simon Horenblas, Bas W. G. van Rhijn, Ekaterina S. Jordanova, Oscar R. Brouwer, Eva Schaake, Michiel S. van der Heijden
Summary: Atezolizumab shows significant antitumor activity in patients with advanced penile cancer, although the 1-year progression-free survival (PFS) did not meet the primary endpoint. Higher PFS is observed in patients with high-risk human papillomavirus-positive tumors and those with high infiltration of intratumoral CD3+CD8+ T cells.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Meeting Abstract
Biophysics
K. Nijssen, K. Westinga, J. Scheepstra, A. Stuut, A. van Rhenen, L. Wagen, L. van Daenen, R. Oostvogels, R. Raymakers, M. de Witte, J. Kuball
BONE MARROW TRANSPLANTATION
(2022)
Meeting Abstract
Biophysics
S. Oerlemans, F. Verheij, T. Nagtegaal-de Wit, K. Nijssen, L. Kramer-Smittenberg, L. Schoonhoven-Bos, A. Van Rhenen, L. Van Hussen-Daenen, L. Van der Wagen, M. De Witte, J. Kuball
BONE MARROW TRANSPLANTATION
(2022)