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3. An IgG‐based bispecific antibody for improved dual targeting in PSMA‐positive cancer

Author

Zekri, Latifa, Vogt, Fabian, Osburg, Lukas, Müller, Stefanie, Kauer, Joseph, Manz, Timo, Pflügler, Martin, Maurer, Andreas, Heitmann, Jonas S, Hagelstein, Ilona, Märklin, Melanie, Hörner, Sebastian, Todenhöfer, Tilmann, Calaminus, Carsten, Stenzl, Arnulf, Pichler, Bernd, la Fougère, Christian, Schneider, Marc A, Rammensee, Hans‐Georg, Zender, Lars, Sipos, Bence, Salih, Helmut R, and Jung, Gundram

Published
2021
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4. IgG-Based Bispecific Anti-CD95 Antibodies for the Treatment of B Cell-Derived Malignancies and Autoimmune Diseases

Author

Hörner, Sebastian, primary, Moustafa-Oglou, Moustafa, additional, Teppert, Karin, additional, Hagelstein, Ilona, additional, Kauer, Joseph, additional, Pflügler, Martin, additional, Neumann, Kristina, additional, Rammensee, Hans-Georg, additional, Metz, Thomas, additional, Herrmann, Andreas, additional, Salih, Helmut R., additional, Jung, Gundram, additional, and Zekri, Latifa, additional

Published
2022
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5. Abstract 2865: CC-3, an IgG-based B7-H3xCD3 bispecific antibody for targeting of gastrointestinal cancers

Author

Zekri, Latifa, primary, Lutz, Martina S., additional, Hagelstein, Ilona, additional, Manz, Timo, additional, Engel, Monika, additional, Klimovich, Boris, additional, Prakash, Nisha, additional, Chashchina, Anna, additional, Hörner, Sebastian, additional, Müller, Stefanie, additional, Märklin, Melanie, additional, Pflügler, Martin, additional, Jung, Gundram, additional, and Salih, Helmut R., additional

Published
2022
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6. A novel IgG-based FLT3xCD3 bispecific antibody for the treatment of AML and B-ALL

Author

Mehta, Naveen K, primary, Pfluegler, Martin, additional, Meetze, Kristan, additional, Li, Bochong, additional, Sindel, Isabelle, additional, Vogt, Fabian, additional, Marklin, Melanie, additional, Heitmann, Jonas S, additional, Kauer, Joseph, additional, Osburg, Lukas, additional, Zekri, Latifa, additional, Bühring, Hans-Jörg, additional, Mueller, Stefanie, additional, Hörner, Sebastian, additional, Baeuerle, Patrick A, additional, Michaelson, Jennifer S, additional, Jung, Gundram, additional, and Salih, Helmut R, additional

Published
2022
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7. CD18 Antibody Application Blocks Unwanted Off-Target T Cell Activation Caused by Bispecific Antibodies

Author

Kauer, Joseph, Vogt, Fabian, Hagelstein, Ilona, Hörner, Sebastian, Märklin, Melanie, Maurer, Stefanie, Salih, Helmut R., Jung, Gundram, and Zekri, Latifa

Subjects
CD18, T cell activation, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, cytokine release syndrome, immunotherapy, bispecific antibodies, Article, RC254-282
Abstract

Simple Summary Bispecific antibodies are a very effective immunotherapy against different types of cancer since they activate T cells in the presence of tumor cells. However, they can cause severe side effects, such as a systemic inflammation called cytokine release syndrome. We aimed to clarify an important mechanism that causes cytokine release syndrome. In cocultures of T cells with endothelial cells or lymphoid cells, application of bispecific antibodies can induce T cell activation and cytokine release in the absence of tumor cells. By blocking the adhesion molecule CD18, this interaction is interrupted and the unwanted T cell activation is diminished. CD18 blockade, however, does not interfere with T cell activation when tumor cells are present. Therefore, CD18 blockade could prevent side effects of bispecific antibodies without decreasing the anti-tumor effect. Abstract T cell-recruiting bispecific antibodies (bsAbs) are successfully used for the treatment of cancer. However, effective treatment with bsAbs is so far hampered by severe side effects, i.e., potentially life-threatening cytokine release syndrome. Off-target T cell activation due to binding of bispecific CD3 antibodies to T cells in the absence of target cells may contribute to excessive cytokine release. We report here, in an in vitro setting, that off-target T cell activation is induced by bsAbs with high CD3 binding affinity and increased by endothelial- or lymphoid cells that act as stimulating bystander cells. Blocking antibodies directed against the adhesion molecules CD18/CD54 or CD2/CD58 markedly reduced this type of off-target T cell activation. CD18 blockade—in contrast to CD2—did not affect the therapeutic activity of various bsAbs. Since CD18 antibodies have been shown to be safely applicable in patients, blockade of this integrin holds promise as a potential target for the prevention of unwanted off-target T cell activation and allows the application of truly effective bsAb doses.

Published
2021

11. An IgG‐based bispecific antibody for improved dual targeting in PSMA‐positive cancer

Author

Zekri, Latifa, primary, Vogt, Fabian, additional, Osburg, Lukas, additional, Müller, Stefanie, additional, Kauer, Joseph, additional, Manz, Timo, additional, Pflügler, Martin, additional, Maurer, Andreas, additional, Heitmann, Jonas S, additional, Hagelstein, Ilona, additional, Märklin, Melanie, additional, Hörner, Sebastian, additional, Todenhöfer, Tilmann, additional, Calaminus, Carsten, additional, Stenzl, Arnulf, additional, Pichler, Bernd, additional, Fougère, Christian, additional, Schneider, Marc A, additional, Rammensee, Hans‐Georg, additional, Zender, Lars, additional, Sipos, Bence, additional, Salih, Helmut R, additional, and Jung, Gundram, additional

Published
2020
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14. Biofunctionalization of Silsesquioxane Nanoparticles

Author

Hörner, Sebastian and Hörner, Sebastian

Abstract

Cube-octameric silsesquioxanes (COSS) were investigated as modular scaffolds for the application in biomedical engineering and associated research areas. Chemical modification of these unique organic-inorganic hybrids endowed them with novel features, aimed at functional tailoring towards executing certain biologic tasks. The chemical and structural peculiarities of COSS nanoparticles were used to address two parallel issues, the first one being development of a viable route to peptide multimers, and the second one – elaboration of a molecular platform for efficient cellular transport.

Published
2017

16. Cosmology

Author

von Hoerner, Sebastian, Verschuur, Gerrit L., editor, and Kellermann, Kenneth I., editor

Published
1974
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28. Nanoscale Biodegradable Organic-Inorganic Hybrids for Efficient Cell Penetration and Drug Delivery.

Author

Hörner S, Knauer S, Uth C, Jöst M, Schmidts V, Frauendorf H, Thiele CM, Avrutina O, and Kolmar H

Subjects
Antineoplastic Agents chemistry, Antineoplastic Agents metabolism, Cell Survival drug effects, Cell-Penetrating Peptides chemistry, Cell-Penetrating Peptides metabolism, Doxorubicin chemistry, Doxorubicin metabolism, Flow Cytometry, HeLa Cells, Humans, Microscopy, Confocal, Molecular Structure, Organosilicon Compounds chemistry, Organosilicon Compounds metabolism, Antineoplastic Agents pharmacology, Cell-Penetrating Peptides pharmacology, Doxorubicin pharmacology, Drug Delivery Systems, Organosilicon Compounds pharmacology
Abstract

We report a comprehensive study on novel, highly efficient, and biodegradable hybrid molecular transporters. To this end, we designed a series of cell-penetrating, cube-octameric silsesquioxanes (COSS), and investigated cellular uptake by confocal microscopy and flow cytometry. A COSS with dense spatial arrangement of guanidinium groups displayed fast uptake kinetics and cell permeation at nanomolar concentrations in living HeLa cells. Efficient uptake was also observed in bacteria, yeasts, and archaea. The COSS-based carrier was significantly more potent than cell-penetrating peptides (CPPs) and displayed low toxicity. It efficiently delivered a covalently attached cytotoxic drug, doxorubicin, to living tumor cells. As the uptake of fluorescently labeled carrier remained in the presence of serum, the system could be considered particularly attractive for the in vivo delivery of therapeutics., (© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Published
2016
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29. A chemoenzymatic approach to protein immobilization onto crystalline cellulose nanoscaffolds.

Author

Uth C, Zielonka S, Hörner S, Rasche N, Plog A, Orelma H, Avrutina O, Zhang K, and Kolmar H

Subjects
Humans, Models, Molecular, Nanoparticles ultrastructure, Oximes chemistry, Peptides chemistry, Surface Properties, Cellulose chemistry, Immobilized Proteins chemistry, Nanoparticles chemistry
Abstract

The immobilization of bioactive molecules onto nanocellulose leads to constructs that combine the properties of the grafted compounds with the biocompatibility and low cytotoxicity of cellulose carriers and the advantages given by their nanometer dimensions. However, the methods commonly used for protein grafting suffer from lack of selectivity, long reaction times, nonphysiological pH ranges and solvents, and the necessity to develop a tailor-made reaction strategy for each individual case. To overcome these restrictions, a generic two-step procedure was developed that takes advantage of the highly efficient oxime ligation combined with enzyme-mediated protein coupling onto the surface of peptide-modified crystalline nanocellulose. The described method is based on efficient and orthogonal transformations, requires no organic solvents, and takes place under physiological conditions. Being site-directed and regiospecific, it could be applied to a vast number of functional proteins., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Published
2014
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30. Cube-octameric silsesquioxane-mediated cargo peptide delivery into living cancer cells.

Author

Hörner S, Fabritz S, Herce HD, Avrutina O, Dietz C, Stark RW, Cardoso MC, and Kolmar H

Subjects
Chromatography, High Pressure Liquid, HeLa Cells, Humans, Microscopy, Atomic Force, Molecular Structure, Nanoparticles chemistry, Particle Size, Peptides chemistry, Peptides genetics, Proliferating Cell Nuclear Antigen chemistry, Proliferating Cell Nuclear Antigen genetics, Proliferating Cell Nuclear Antigen metabolism, Drug Delivery Systems, Organosilicon Compounds chemistry, Peptides metabolism, Quaternary Ammonium Compounds chemistry
Abstract

Cube octameric silsesquioxanes (COSS) are among the smallest nanoparticles known to date with a diameter of only 0.7 nm. We describe a COSS-based delivery system which allows for the drug targeting in human cells. It comprises a siloxane core with seven pendant aminopropyl groups and a fluorescently labeled peptidic ligand attached to one cage corner via a reversible disulfide bond to ensure its intracellular release. Bimodal amplitude-modulated atomic force microscopy (AFM) experiments revealed the formation of dendritic COSS structures by a self-assembly of single particles on negatively charged surfaces. Nuclear targeting was demonstrated in HeLa cells by selective binding of released p21(Cip1/Waf1)-derived cargo peptide to PCNA, a protein involved in DNA replication and repair.

Published
2013
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