Article
Biology
Gerald Willimsky, Christin Beier, Lena Immisch, George Papafotiou, Vivian Scheuplein, Andrean Goede, Hermann-Georg Holzhuetter, Thomas Blankenstein, Peter M. Kloetzel
Summary: Proteasome-catalyzed peptide splicing (PCPS) can generate attractive neoepitopes for T cell receptor (TCR)-based adoptive T cell therapy, but in vivo experiments failed to detect any specific T cell response to these neo-splicetopes and provided no evidence that they were naturally processed and presented. Additionally, only one of the predicted neo-splicetopes was generated in vitro by PCPS, raising questions about the reliability of algorithms and in vitro reactions for simulating in vivo splicing.
Article
Chemistry, Organic
Martin Kurfirt, Cervenkova St'astna Lucie, Petra Curinova, Vojtech Hamala, Jindrich Karban
Summary: The Tn antigen, commonly found in tumors but rare in healthy tissues, may be a promising target for antitumor immunotherapy. Its low immunogenicity can potentially be enhanced through deoxyfluorination of the GalNAc moiety.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Antonius A. de Waard, Tamara Verkerk, Kelly Hoefakker, Dirk M. van der Steen, Marlieke L. M. Jongsma, Dganit Melamed Kadosh, Sophie Bliss, Arnoud H. de Ru, Arie Admon, Peter A. van Veelen, Marieke Griffioen, Mirjam H. M. Heemskerk, Robbert M. Spaapen
Summary: The absence of clinically relevant antigens on healthy cells needs to be extensively tested in order to define safe targets for T cell-based immunotherapy.
Article
Oncology
Zaki Molvi, Martin G. Klatt, Tao Dao, Jessica Urraca, David A. Scheinberg, Richard J. O'Reilly
Summary: This study identified phosphopeptides presented by different alleles on tumors, which could be targeted for cancer immunotherapy, but the immunogenicity of these phosphopeptides is not consistent. While phosphopeptides presented by HLA-A*02:01 and A*11:01 were consistently immunogenic, those presented by HLA-A*03:01 and C*07:01, although properly presented, were not. This indicates the need to consider allele-specific differences in phosphopeptide-targeted immunotherapies to address a broader patient population.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Oncology
Francois Anna, Elodie Bole-Richard, Joel LeMaoult, Marie Escande, Martin Lecomte, Jean-Made Certoux, Philippe Souque, Francine Garnache, Olivier Adotevi, Pierre Langlade-Demoyen, Maria Loustau, Julien Caumartin
Summary: CAR-T cell immunotherapy is a breakthrough in treating hematological malignancies, but the lack of tumor-specific antigens and immunosuppressive tumor microenvironments remain major hurdles. A new study shows that HLA-G, acting as both an immune checkpoint and a tumor-specific antigen, could be a promising target for CAR-T cell therapy.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Review
Immunology
Joseph J. Barchi
Summary: For many years, cell-surface glycans have been an important target for anticancer immunotherapy. Recent advances in immunotherapy have led to significant outcomes in some patients. However, there is a need for improved therapeutics and delivery techniques. Glycan-based targets are gaining popularity and nanotechnology can enhance drug delivery.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Yang Liu, Bohan Li, Xiujing Zheng, Decai Xiong, Xinshan Ye
Summary: KH-1 is a valuable target for antitumor vaccines, but most TACAs tend to induce immunological tolerance. To overcome this, fluorinated derivatives of KH-1 were designed and conjugated to CRM197 to form glycoconjugates. These modified KH-1 conjugates were found to induce higher titers of antibodies, particularly IgG, which can recognize and eliminate KH-1-positive cancer cells through CDC. The trifluoro-modified KH-1-TF-CRM197 shows great potential as an anticancer vaccine candidate.
Article
Medicine, Research & Experimental
Katarina Madunic, Oleg A. Mayboroda, Tao Zhang, Julia Weber, Geert-Jan Boons, Hans Morreau, Ronald van Vlierberghe, Tom van Wezel, Guinevere S. M. Lageveen-Kammeijer, Manfred Wuhrer
Summary: Cells are covered with a dense layer of carbohydrates, some of which are solely present on neoplastic cells. The so-called tumor-associated carbohydrate antigens (TACAs) are increasingly recognized as promising targets for immunotherapy. These carbohydrates differ from those of the surrounding non-cancerous tissues and contribute to the malignant phenotype of the cancer cells by promoting proliferation, metastasis, and immunosuppression. However, due to tumor tissue heterogeneity and technological limitations, TACAs are insufficiently explored. In this study, a workflow was established to analyze the colorectal cancer (CRC)-associated O-linked glycans. Distinctive O-glycosylation features were found in cancerous, stromal, and normal colon mucosal regions. Over 100 O-linked glycans were detected in cancerous regions with absence in normal mucosa. A novel panel of highly specific TACAs, based upon differences in the glycomic profiles between CRC and healthy colon mucosa, were identified. These TACAs could be potential targets for innovative cancer immune target therapies and lay the foundation for the targeted treatment of CRC.
Review
Chemistry, Medicinal
Faye A. Camp, Jill E. Slansky
Summary: Immunotherapies primarily rely on CD8+ effector T cells to target and eliminate tumor cells, involving adoptive cell therapy and anti-cancer vaccines. The selection of antigens and tumor mutation burden are crucial aspects of T cell-based immunotherapies. Different classes of cancer antigens have varying immunological properties which can influence their utility in immunotherapies.
Article
Oncology
Daniel Kalinovsky, Alexey Kibardin, Irina Kholodenko, Elena Svirshchevskaya, Igor I. Doronin, Mariya Konovalova, Maria Grechikhina, Fedor N. Rozov, Sergey S. Larin, Sergey M. Deyev, Roman Kholodenko
Summary: This study is the first to analyze the cytotoxic activity of anti-GD2 antibody-drug conjugates (ADCs) against solid tumors. The ADCs showed cytotoxic effects in a wide panel of GD2-positive tumor cell lines and demonstrated antitumor effects in mouse models of GD2-positive solid cancer.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Biochemistry & Molecular Biology
Sinthuja Jegatheeswaran, Mickael Guillemineau, Richard Giovane, Louis Borrillo, Liang Liao, Deng Kuir, France-Isabelle Auzanneau
Summary: Insights into the differential binding characteristics of anti-Le(a) and anti-Le(a)Le(x) monoclonal antibodies provide information for the development of Le(a)Le(x)-based cancer immunotherapeutics. The study characterizes the epitope recognized by anti-Le(a) mAb SPM 522 and identifies the major recognition element as the extended hydrophobic surface defined by the Le(a)-beta-D-Gal residue. These findings contribute to a better understanding of the binding properties of anti-Le(a) antibodies and provide a basis for the design of targeted cancer immunotherapy.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Analytical
Xing-Hui Ren, Hai-Yan Wang, Si Li, Xi-Wen He, Wen-You Li, Yu-Kui Zhang
Summary: In this study, Gal-NAc-imprinted nanoparticles were synthesized using a boronate-affinity glycan-oriented surface imprinting strategy. Molecularly imprinted polymers were hybridized with fluorescent silicon nanoparticles for highly sensitive fluorescence and magnetic resonance imaging. The synthesized nanoparticles showed desirable performance in dual-model imaging for specific targeting of cancer cells, with potential in real biological samples.
Article
Psychology, Multidisciplinary
Taylor Elam, Kanako Taku
Summary: This study examines the differences between posttraumatic growth (PTG) and resiliency in terms of their associations with cognitive ability. The results show that perceived PTG is associated with increased emotion recognition ability, while resiliency is negatively related to empathy but not significantly associated with emotion recognition.
FRONTIERS IN PSYCHOLOGY
(2022)
Article
Oncology
Luan Sun, Fang Gao, Zhanhui Gao, Lei Ao, Na Li, Sujuan Ma, Meng Jia, Nan Li, Peihua Lu, Beicheng Sun, Mitchell Ho, Shaochang Jia, Tong Ding, Wei Gao
Summary: This study constructed two types of CAR-T cells targeting different epitopes of GPC3 to investigate the influence of sGPC3 on the activation and cytotoxicity of CAR-T cells in vitro and in vivo. Results showed that sGPC3 significantly inhibited the release of cytokines and the cytotoxicity of anti-GPC3 CAR-T cells in vitro, and in mouse models sGPC3 expression in Hep3B xenograft tumors led to a worse response to CAR-T cell treatment.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Oncology
Siri Amanda Tvingsholm, Marcus Svensson Frej, Vibeke Mindahl Rafa, Ulla Kring Hansen, Maria Ormhoj, Alexander Tyron, Agnete W. P. Jensen, Mohammad Kadivar, Amalie Kai Bentzen, Kamilla K. Munk, Gitte N. Aasbjerg, Jeppe S. H. Ternander, Christina Heeke, Tripti Tamhane, Christian Schmess, Samuel A. Funt, Julie Westerlin Kjeldsen, Anders Handrup Kverneland, Ozcan Met, Arianna Draghi, Soren Nyboe Jakobsen, Marco Donia, Inge Marie Svane, Sine Reker Hadrup
Summary: In this study, a novel technology called artificial antigen-presenting scaffolds (Ag-scaffolds) was developed for ex vivo expansion of antigen-specific T-cells. By optimizing the stoichiometry of TCR engaging moieties (pMHC) and stimulatory moieties (cytokines), the desired characteristics of T-cells were obtained. This technology shows great promise for selective expansion of antigen-specific CD8+ T cells and can be used for adoptive cell therapy.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Veterinary Sciences
Sergio Villanueva-Saz, Marivi Martinez, Jacobo Giner, Ana Gonzalez, Ana Pilar Tobajas, Maria Dolores Perez, Erandi Lira-Navarrete, Andres Manuel Gonzalez-Ramirez, Javier Macias-Leon, Maite Verde, Andres Yzuel, Ramon Hurtado-Guerrero, Maykel Arias, Llipsy Santiago, Jordi Aguilo-Gisbert, Hector Ruiz, Delia Lacasta, Diana Marteles, Antonio Fernandez
Summary: The study finds that stray cats have a minimal role in the transmission of SARS-CoV-2, and there is no increase in seropositivity during different waves of COVID-19 outbreaks in this group of animals. Additionally, stray cats also have multiple co-infections including infectious peritonitis, heartworm disease, and feline immunodeficiency virus. Further epidemiological surveillance is needed to determine the risk that other animals may possess, even though stray cats do not seem to play a role in transmission.
VETERINARY RESEARCH COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Emma Scott, Kirsty Hodgson, Beatriz Calle, Helen Turner, Kathleen Cheung, Abel Bermudez, Fernando Jose Garcia Marques, Hayley Pye, Edward Christopher Yo, Khirul Islam, Htoo Zarni Oo, Urszula L. McClurg, Laura Wilson, Huw Thomas, Fiona M. Frame, Margarita Orozco-Moreno, Kayla Bastian, Hector M. Arredondo, Chloe Roustan, Melissa Anne Gray, Lois Kelly, Aaron Tolson, Ellie Mellor, Gerald Hysenaj, Emily Archer Goode, Rebecca Garnham, Adam Duxfield, Susan Heavey, Urszula Stopka-Farooqui, Aiman Haider, Alex Freeman, Saurabh Singh, Edward W. Johnston, Shonit Punwani, Bridget Knight, Paul McCullagh, John McGrath, Malcolm Crundwell, Lorna Harries, Denisa Bogdan, Daniel Westaby, Gemma Fowler, Penny Flohr, Wei Yuan, Adam Sharp, Johann de Bono, Norman J. Maitland, Simon Wisnovsky, Carolyn R. Bertozzi, Rakesh Heer, Ramon Hurtado Guerrero, Mads Daugaard, Janne Leivo, Hayley Whitaker, Sharon Pitteri, Ning Wang, David J. Elliott, Benjamin Schumann, Jennifer Munkley
Summary: Prostate cancer is the leading cancer among men, causing over 350,000 deaths worldwide annually. This study reveals that the glycosyltransferase enzyme GALNT7 is upregulated in prostate cancer tissue and can be used as a biomarker to diagnose the disease with higher accuracy than the traditional PSA test. Additionally, GALNT7 is found to play a role in promoting prostate tumor growth and is associated with cell cycle and immune signaling pathways. Overall, this study highlights the importance of GALNT7-mediated O-glycosylation in prostate cancer progression.
Review
Chemistry, Multidisciplinary
Ignacio Sanz-Martinez, Sandra Pereira, Pedro Merino, Francisco Corzana, Ramon Hurtado-Guerrero
Summary: N-acetylgalactosamine (GalNAc) type O-glycosylation is a crucial posttranslational modification in biology. Malfunction of this modification is associated with truncated O-glycans in cancer. Understanding the structure and recognition of GalNAc-containing glycopeptides can contribute to the development of therapeutic vaccines and new diagnostic tools for cancer detection.
ACCOUNTS OF CHEMICAL RESEARCH
(2023)
Article
Nanoscience & Nanotechnology
Anna Blasi-Romero, Molly Angstrom, Antonio Franconetti, Taj Muhammad, Jesus Jimenez-Barbero, Ulf Goransson, Carlos Palo-Nieto, Natalia Ferraz
Summary: This study combines the wound-healing properties of KR-12 peptide with wood-derived cellulose nanofibrils (CNFs) to create bioactive materials for treating chronic wounds. Different coupling chemistries were used to covalently attach KR-12 derivatives onto CNFs, and the bioactivity of KR12-CNF conjugates was evaluated in terms of antibacterial activities and anti-inflammatory effects. The results showed that thiol-ene chemistry produced the most bioactive conjugates, attributed to favorable peptide conformation and accessibility. This study advances the development of CNF-based materials for chronic wound care and provides insights into the effect of conjugation chemistry on the bioactivity of host defense peptides.
ACS APPLIED MATERIALS & INTERFACES
(2023)
Article
Veterinary Sciences
Sergio Villanueva-Saz, Marivi Martinez, Pablo Rueda, Sara Bolea, Maria Dolores Perez, Maite Verde, Andres Yzuel, Ramon Hurtado-Guerrero, Julian Pardo, Llipsy Santiago, Antonio Fernandez, Maykel Arias
Summary: This study reports the detection and monitoring of SARS-CoV-2 antibodies in cats under natural conditions. The results show that these antibodies can persist for more than 16 months and reinfection is possible. The study confirms a gradual decrease in the immune response to SARS-CoV-2 in cats, but reinfection can stimulate an increase in immunity.
VETERINARY RESEARCH COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Itxaso Anso, Andreas Naegeli, Javier O. Cifuente, Ane Orrantia, Erica Andersson, Olatz Zenarruzabeitia, Alicia Moraleda-Montoya, Mikel Garcia-Alija, Francisco Corzana, Rafael A. Del Orbe, Francisco Borrego, Beatriz Trastoy, Jonathan Sjogren, Marcelo E. Guerin
Summary: Red blood cell antigens are critical in blood transfusion. Researchers have discovered a bacterial enzyme called FucOB that can convert universal O type blood into the rare Bombay type blood. This finding has the potential to facilitate transfusion in recipients with the Bombay phenotype.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Maria Pia Lenza, Leire Egia-Mendikute, Asier Antonana-Vildosola, Catia O. Soares, Helena Coelho, Francisco Corzana, Alexandre Bosch, Prodhi Manisha, Jon Imanol Quintana, Iker Oyenarte, Luca Unione, Maria Jesus Moure, Mikel Azkargorta, Unai Atxabal, Klaudia Sobczak, Felix Elortza, James D. Sutherland, Rosa Barrio, Filipa Marcelo, Jesus Jimenez-Barbero, Asis Palazon, June Ereno-Orbea
Summary: This study elucidates the structure and binding epitope of Siglec-15, providing insights into its mechanism of action and potential for cancer immunotherapy. The findings highlight the importance of glycosylation in controlling T cell responses and identify CD11b as a binding partner for Siglec-15 on human T cells.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Beatriz Piniello, Javier Macias-Leon, Shun Miyazaki, Ana Garcia-Garcia, Ismael Companon, Mattia Ghirardello, Victor Taleb, Billy Veloz, Francisco Corzana, Atsushi Miyagawa, Carme Rovira, Ramon Hurtado-Guerrero
Summary: In this study, the structures of soluble HMW1C-like N-glycosyltransferases (NGTs) were reported, revealing a key dyad of basic/acidic residues that plays a crucial role in Asn catalysis. The study also found that UDP-galactose and UDP-glucose mimetics act as poor substrates and inhibitors, impeding catalysis. QM/MM simulations provide insight into the reaction mechanism of AaNGT. These findings are important for understanding the mechanism of NGTs and designing drugs.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Gerard Baquer, Lluc Semente, Pere Rafols, Lucia Martin-Saiz, Christoph Bookmeyer, Jose A. Fernandez, Xavier Correig, Maria Garcia-Altares
Summary: Matrix-Assisted Laser Desorption Ionization Mass Spectrometry Imaging (MALDI-MSI) can spatially analyze the chemical composition of tissues, with a particular focus on lipids. However, lipid identification in MALDI-MSI is challenging due to the lack of chromatographic separation or untargeted tandem mass spectrometry. In this study, researchers developed an open-source R package called rMSIfragment, which utilizes known adducts and fragmentation pathways to confidently annotate lipids in MALDI-MSI. The package achieved high annotation accuracy in validation experiments.
JOURNAL OF CHEMINFORMATICS
(2023)
Article
Chemistry, Physical
Michael Eichenberger, Thomas Schwander, Sean Hueppi, Jan Kreuzer, Peer R. E. Mittl, Francesca Peccati, Gonzalo Jimenez-Oses, Michael Naesby, Rebecca M. Buller
Summary: Anthocyanin-related glutathione transferases, traditionally known for their role in anthocyanin transport, have been found to catalyze a crucial dehydration reaction in anthocyanin synthesis. By introducing these enzymes into baker's yeast, researchers achieved a significant increase in anthocyanin production. This discovery not only sheds light on the biosynthesis of anthocyanins but also holds potential for microbial production of colorants and improvements in industrial and ornamental plant breeding.
Review
Chemistry, Multidisciplinary
Jon I. Quintana, Unai Atxabal, Luca Unione, Ana Arda, Jesus Jimenez-Barbero
Summary: Nuclear Magnetic Resonance (NMR) is widely used to study glycan-protein molecular recognition events, providing qualitative and quantitative information at different levels of resolution and complexity. However, the weak affinity of lectin-sugar interactions is overcome by multivalency in biological processes. The application of NMR methods to monitor multivalent lectin-glycan interactions is challenging due to the disappearance of NMR signals when large macromolecular complexes are formed.
CHEMICAL SOCIETY REVIEWS
(2023)
Article
Chemistry, Multidisciplinary
Carlo Pifferi, Leire Aguinagalde, Ane Ruiz-de-Angulo, Nagore Sacristan, Priscila Tonon Baschirotto, Ana Poveda, Jesus Jimenez-Barbero, Juan Anguita, Alberto Fernandez-Tejada
Summary: The overexpression of aberrantly glycosylated tumor-associated mucin-1 (TA-MUC1) in human cancers makes it a major target for the development of anticancer vaccines derived from synthetic MUC1-(glyco)peptide antigens. However, glycopeptide-based subunit vaccines are weakly immunogenic, requiring adjuvants and/or additional immunopotentiating approaches to generate optimal immune responses.
Article
Biochemistry & Molecular Biology
Collin J. Ballard, Miya R. Paserba, Earnest James Paul Daniel, Ramon Hurtado-Guerrero, Thomas A. Gerken
Summary: A large family of polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts) play a crucial role in mucin O-glycosylation. The study reveals the importance of flanking charged residues in determining the substrate specificity of GalNAc-Ts. Different isoforms of GalNAc-Ts exhibit diverse charge specificities, and even isoforms with high sequence identity can have different charge preferences. These electrostatic interactions impact substrate binding and orientation on the enzyme surface, thus modulating their activities.