Niosomes as Biocompatible Scaffolds for the Multivalent Presentation of Tumor-Associated Antigens (TACAs) to the Immune System

Fully synthetic tumor-associated carbohydrate antigen (TACA)-based vaccines are a promising strategy to treat cancer. To overcome the intrinsic low immunogenicity of TACAs, the choice of the antigens’ analogues and multivalent presentation have been proved to be successful. Here, we present the preparation, characterization, and in vitro screening of niosomes displaying multiple copies of the mucin antigen TnThr (niosomes-7) or of TnThr mimetic 1 (niosomes-2). Unprecedentedly, structural differences, likely related to the carbohydrate portions, were observed for the two colloidal systems. Both niosomal systems are stable, nontoxic and endowed with promising immunogenic properties.

[1]  P. Besenius,et al.  The Development of Vaccines from Synthetic Tumor‐Associated Mucin Glycopeptides and their Glycosylation‐Dependent Immune Response , 2021, Chemical record.

[2]  C. Rosano,et al.  Modulation of immune responses using adjuvants to facilitate therapeutic vaccination , 2020, Immunological reviews.

[3]  F. Gabel,et al.  A Structurally Simple Vaccine Candidate Reduces Progression and Dissemination of Triple-Negative Breast Cancer , 2020, iScience.

[4]  C. Alfaro,et al.  RETRACTED ARTICLE: Significance of the IL-8 pathway for immunotherapy , 2019, Human vaccines & immunotherapeutics.

[5]  A. Becchetti,et al.  Niosomal Formulation of a Lipoyl-Carnosine Derivative Targeting TRPA1 Channels in Brain , 2019, Pharmaceutics.

[6]  Laura R. Sadofsky,et al.  Characterisation of a New Human Alveolar Macrophage-Like Cell Line (Daisy) , 2019, Lung.

[7]  J. Wang,et al.  Liposomal Antitumor Vaccines Targeting Mucin 1 Elicit a Lipid-Dependent Immunodominant Response. , 2019, Chemistry, an Asian journal.

[8]  R. Fiammengo,et al.  Structure-Based Design of Potent Tumor-Associated Antigens: Modulation of Peptide Presentation by Single-Atom O/S or O/Se Substitutions at the Glycosidic Linkage. , 2019, Journal of the American Chemical Society.

[9]  M. Najafi,et al.  Macrophage polarity in cancer: A review , 2018, Journal of cellular biochemistry.

[10]  J. T. Afshari,et al.  Macrophage plasticity, polarization, and function in health and disease , 2018, Journal of cellular physiology.

[11]  F. Marincola,et al.  Unleashing endogenous TNF-alpha as a cancer immunotherapeutic , 2018, Journal of Translational Medicine.

[12]  S. Lucas,et al.  Proton irradiation orchestrates macrophage reprogramming through NFκB signaling , 2018, Cell Death & Disease.

[13]  P. Seeberger,et al.  Synthesis, Liposomal Formulation, and Immunological Evaluation of a Minimalistic Carbohydrate-α-GalCer Vaccine Candidate. , 2018, Journal of medicinal chemistry.

[14]  X. Ye,et al.  Carbohydrate‐based vaccines for oncotherapy , 2018, Medicinal research reviews.

[15]  S. Mathivanan,et al.  Secreted Tumor Antigens – Immune Biomarkers for Diagnosis and Therapy , 2017, Proteomics.

[16]  M. Cnop,et al.  Stearic acid at physiologic concentrations induces in vitro lipotoxicity in circulating angiogenic cells. , 2017, Atherosclerosis.

[17]  D. Passeri,et al.  Niosomal approach to brain delivery: Development, characterization and in vitro toxicological studies. , 2016, International journal of pharmaceutics.

[18]  C. Foged,et al.  Trehalose diester glycolipids are superior to the monoesters in binding to Mincle, activation of macrophages in vitro and adjuvant activity in vivo , 2016, Innate immunity.

[19]  J. Munkley The Role of Sialyl-Tn in Cancer , 2016, International journal of molecular sciences.

[20]  Yifa Zhou,et al.  Synthesis and immunological evaluation of N-acyl modified Tn analogues as anticancer vaccine candidates. , 2016, Bioorganic & medicinal chemistry.

[21]  F. Cañada,et al.  Structural Insights into the Binding of Sugar Receptors (Lectins) to a Synthetic Tricyclic Tn Mimetic and Its Glycopeptide Version , 2015 .

[22]  M. Raes,et al.  M1 and M2 macrophages derived from THP-1 cells differentially modulate the response of cancer cells to etoposide , 2015, BMC Cancer.

[23]  J. Taylor‐Papadimitriou,et al.  The Breast Cancer-Associated Glycoforms of MUC1, MUC1-Tn and sialyl-Tn, Are Expressed in COSMC Wild-Type Cells and Bind the C-Type Lectin MGL , 2015, PloS one.

[24]  L. BenMohamed,et al.  A cancer therapeutic vaccine based on clustered Tn-antigen mimetics induces strong antibody-mediated protective immunity. , 2014, Angewandte Chemie.

[25]  O. Renaudet,et al.  Recent progress in antitumoral synthetic vaccines. , 2014, ACS medicinal chemistry letters.

[26]  Spencer J. Williams,et al.  MCL and Mincle: C-Type Lectin Receptors That Sense Damaged Self and Pathogen-Associated Molecular Patterns , 2014, Front. Immunol..

[27]  Y. Kooyk,et al.  MGL signaling augments TLR2‐mediated responses for enhanced IL‐10 and TNF‐α secretion , 2013, Journal of leukocyte biology.

[28]  G. Zaccai,et al.  Change of dynamics of raft-model membrane induced by amyloid-β protein binding , 2013, The European physical journal. E, Soft matter.

[29]  J. Panee Monocyte Chemoattractant Protein 1 (MCP-1) in obesity and diabetes. , 2012, Cytokine.

[30]  P. Vogel,et al.  A C-linked disaccharide analogue of Thomsen-Friedenreich epitope induces a strong immune response in mice. , 2012, Chemistry.

[31]  Alberto Mantovani,et al.  Orchestration of metabolism by macrophages. , 2012, Cell metabolism.

[32]  C. Ghelardini,et al.  Development and characterization of niosomal formulations of doxorubicin aimed at brain targeting. , 2012, Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques.

[33]  G. P. Kumar,et al.  Nonionic surfactant vesicular systems for effective drug delivery—an overview , 2011 .

[34]  Yup Kang,et al.  Capsaicin attenuates palmitate-induced expression of macrophage inflammatory protein 1 and interleukin 8 by increasing palmitate oxidation and reducing c-Jun activation in THP-1 (human acute monocytic leukemia cell) cells. , 2011, Nutrition research.

[35]  J. Mes,et al.  Transcription profiles of LPS-stimulated THP-1 monocytes and macrophages: a tool to study inflammation modulating effects of food-derived compounds. , 2010, Food & function.

[36]  Anja Hoffmann-Röder,et al.  Synthetische Antitumorvakzine aus Tetanus‐Toxoid‐Konjugaten von MUC1‐Glycopeptiden mit Thomsen‐Friedenreich‐Antigen und dessen fluorsubstituiertem Analogon , 2010 .

[37]  Dennis R. Burton,et al.  Carbohydrate vaccines: developing sweet solutions to sticky situations? , 2010, Nature Reviews Drug Discovery.

[38]  Marc Daigneault,et al.  The Identification of Markers of Macrophage Differentiation in PMA-Stimulated THP-1 Cells and Monocyte-Derived Macrophages , 2010, PloS one.

[39]  X. Yao,et al.  Controlled evolution from multilamellar vesicles to hexagonal mesostructures through the addition of 1,3,5-trimethylbenzene. , 2009, Journal of colloid and interface science.

[40]  L. Legnani,et al.  Cyclic glycopeptidomimetics through a versatile sugar-based scaffold. , 2009, Bioorganic & medicinal chemistry letters.

[41]  F. Sánchez-Jiménez,et al.  Monocyte chemoattractant protein-1: a key mediator in inflammatory processes. , 2009, The international journal of biochemistry & cell biology.

[42]  O. Wiklund,et al.  Induction of proinflammatory cytokines by long-chain saturated fatty acids in human macrophages. , 2009, Atherosclerosis.

[43]  C. Ohyama Glycosylation in bladder cancer , 2008, International Journal of Clinical Oncology.

[44]  K. K. Mong,et al.  Versatile acetylation of carbohydrate substrates with bench-top sulfonic acids and application to one-pot syntheses of peracetylated thioglycosides. , 2008, Carbohydrate research.

[45]  J. Zou,et al.  Structure transition from hexagonal mesostructured rodlike silica to multilamellar vesicles. , 2008, Langmuir : the ACS journal of surfaces and colloids.

[46]  L. Legnani,et al.  Synthesis, Conformational Studies, Binding Assessment and Liposome Insertion of a Thioether‐Bridged Mimetic of the Antigen GM3 Ganglioside Lactone , 2007, Chembiochem : a European journal of chemical biology.

[47]  G. Zaccai,et al.  How soft is a protein? A protein dynamics force constant measured by neutron scattering. , 2000, Science.

[48]  J. Taylor‐Papadimitriou,et al.  Comparison of O-Linked Carbohydrate Chains in MUC-1 Mucin from Normal Breast Epithelial Cell Lines and Breast Carcinoma Cell Lines: , 1996, The Journal of Biological Chemistry.

[49]  H. Paulsen,et al.  Synthese von L-Prolin-haltigen O-Glycopeptiden , 1990 .