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Your search keyword '"Ralf J. Hosse"' showing total 15 results
Start Over Author "Ralf J. Hosse" Publisher american association for cancer research (aacr)
15 results on '"Ralf J. Hosse"'

1. Supplementary Methods from RG7386, a Novel Tetravalent FAP-DR5 Antibody, Effectively Triggers FAP-Dependent, Avidity-Driven DR5 Hyperclustering and Tumor Cell Apoptosis

Author

Pablo Umaña, Klaus Bosslet, Christian Klein, Suzana Vega-Harring, Gary Xu, Peng Wang, Bin Liu, Cuiying Shao, Hadassah Sade, Werner Scheuer, Frank Herting, Thomas G. Weber, Ekkehard Mössner, Ralf J. Hosse, Sherif Daouti, Ningping Feng, Kathryn Packman, Huifeng Niu, Valeria Runza, Meher Majety, Barbara Weiser, Claudia Ferrara Koller, Inja Waldhauer, Sandra Grau-Richards, Thomas Friess, Katharina Wartha, and Peter Brünker

Abstract

Supplementary information on cell maintenance, and antibody selection and characterization

Published
2023

2. Supplementary Table S3 from RG7386, a Novel Tetravalent FAP-DR5 Antibody, Effectively Triggers FAP-Dependent, Avidity-Driven DR5 Hyperclustering and Tumor Cell Apoptosis

Author

Pablo Umaña, Klaus Bosslet, Christian Klein, Suzana Vega-Harring, Gary Xu, Peng Wang, Bin Liu, Cuiying Shao, Hadassah Sade, Werner Scheuer, Frank Herting, Thomas G. Weber, Ekkehard Mössner, Ralf J. Hosse, Sherif Daouti, Ningping Feng, Kathryn Packman, Huifeng Niu, Valeria Runza, Meher Majety, Barbara Weiser, Claudia Ferrara Koller, Inja Waldhauer, Sandra Grau-Richards, Thomas Friess, Katharina Wartha, and Peter Brünker

Abstract

FAP-drozitumab antibody-mediated apoptosis does not correlate with DR5.

Published
2023

3. Supplementary Figure S3 from RG7386, a Novel Tetravalent FAP-DR5 Antibody, Effectively Triggers FAP-Dependent, Avidity-Driven DR5 Hyperclustering and Tumor Cell Apoptosis

Author

Pablo Umaña, Klaus Bosslet, Christian Klein, Suzana Vega-Harring, Gary Xu, Peng Wang, Bin Liu, Cuiying Shao, Hadassah Sade, Werner Scheuer, Frank Herting, Thomas G. Weber, Ekkehard Mössner, Ralf J. Hosse, Sherif Daouti, Ningping Feng, Kathryn Packman, Huifeng Niu, Valeria Runza, Meher Majety, Barbara Weiser, Claudia Ferrara Koller, Inja Waldhauer, Sandra Grau-Richards, Thomas Friess, Katharina Wartha, and Peter Brünker

Abstract

Characterization and optimization of RG7386 dosing in vivo.

Published
2023

4. Data from RG7386, a Novel Tetravalent FAP-DR5 Antibody, Effectively Triggers FAP-Dependent, Avidity-Driven DR5 Hyperclustering and Tumor Cell Apoptosis

Author

Pablo Umaña, Klaus Bosslet, Christian Klein, Suzana Vega-Harring, Gary Xu, Peng Wang, Bin Liu, Cuiying Shao, Hadassah Sade, Werner Scheuer, Frank Herting, Thomas G. Weber, Ekkehard Mössner, Ralf J. Hosse, Sherif Daouti, Ningping Feng, Kathryn Packman, Huifeng Niu, Valeria Runza, Meher Majety, Barbara Weiser, Claudia Ferrara Koller, Inja Waldhauer, Sandra Grau-Richards, Thomas Friess, Katharina Wartha, and Peter Brünker

Abstract

Dysregulated cellular apoptosis and resistance to cell death are hallmarks of neoplastic initiation and disease progression. Therefore, the development of agents that overcome apoptosis dysregulation in tumor cells is an attractive therapeutic approach. Activation of the extrinsic apoptotic pathway is strongly dependent on death receptor (DR) hyperclustering on the cell surface. However, strategies to activate DR5 or DR4 through agonistic antibodies have had only limited clinical success. To pursue an alternative approach for tumor-targeted induction of apoptosis, we engineered a bispecific antibody (BsAb), which simultaneously targets fibroblast-activation protein (FAP) on cancer-associated fibroblasts in tumor stroma and DR5 on tumor cells. We hypothesized that bivalent binding to both FAP and DR5 leads to avidity-driven hyperclustering of DR5 and subsequently strong induction of apoptosis in tumor cells but not in normal cells. Here, we show that RG7386, an optimized FAP-DR5 BsAb, triggers potent tumor cell apoptosis in vitro and in vivo in preclinical tumor models with FAP-positive stroma. RG7386 antitumor efficacy was strictly FAP dependent, was independent of FcR cross-linking, and was superior to conventional DR5 antibodies. In combination with irinotecan or doxorubicin, FAP-DR5 treatment resulted in substantial tumor regression in patient-derived xenograft models. FAP-DR5 also demonstrated single-agent activity against FAP-expressing malignant cells, due to cross-binding of FAP and DR5 across tumor cells. Taken together, these data demonstrate that RG7386, a novel and potent antitumor agent in both mono- and combination therapies, overcomes limitations of previous DR5 antibodies and represents a promising approach to conquer tumor-associated resistance to apoptosis. Mol Cancer Ther; 15(5); 946–57. ©2016 AACR.

Published
2023

5. Supplementary Figure S2 and Table S4 from RG7386, a Novel Tetravalent FAP-DR5 Antibody, Effectively Triggers FAP-Dependent, Avidity-Driven DR5 Hyperclustering and Tumor Cell Apoptosis

Author

Pablo Umaña, Klaus Bosslet, Christian Klein, Suzana Vega-Harring, Gary Xu, Peng Wang, Bin Liu, Cuiying Shao, Hadassah Sade, Werner Scheuer, Frank Herting, Thomas G. Weber, Ekkehard Mössner, Ralf J. Hosse, Sherif Daouti, Ningping Feng, Kathryn Packman, Huifeng Niu, Valeria Runza, Meher Majety, Barbara Weiser, Claudia Ferrara Koller, Inja Waldhauer, Sandra Grau-Richards, Thomas Friess, Katharina Wartha, and Peter Brünker

Abstract

Figure S2. Related to Figure 3. In vitro characterization of the FAP-DR5 BsAb RG7386; Table S4. Characterization of RG7386 binding avidities.

Published
2023

6. Supplementary Figure S4 from RG7386, a Novel Tetravalent FAP-DR5 Antibody, Effectively Triggers FAP-Dependent, Avidity-Driven DR5 Hyperclustering and Tumor Cell Apoptosis

Author

Pablo Umaña, Klaus Bosslet, Christian Klein, Suzana Vega-Harring, Gary Xu, Peng Wang, Bin Liu, Cuiying Shao, Hadassah Sade, Werner Scheuer, Frank Herting, Thomas G. Weber, Ekkehard Mössner, Ralf J. Hosse, Sherif Daouti, Ningping Feng, Kathryn Packman, Huifeng Niu, Valeria Runza, Meher Majety, Barbara Weiser, Claudia Ferrara Koller, Inja Waldhauer, Sandra Grau-Richards, Thomas Friess, Katharina Wartha, and Peter Brünker

Abstract

FAP-drozitumab BsAb induces tumor growth inhibition in vivo.

Published
2023

7. Supplementary Figure S1, Table S1, and Table S2 from RG7386, a Novel Tetravalent FAP-DR5 Antibody, Effectively Triggers FAP-Dependent, Avidity-Driven DR5 Hyperclustering and Tumor Cell Apoptosis

Author

Pablo Umaña, Klaus Bosslet, Christian Klein, Suzana Vega-Harring, Gary Xu, Peng Wang, Bin Liu, Cuiying Shao, Hadassah Sade, Werner Scheuer, Frank Herting, Thomas G. Weber, Ekkehard Mössner, Ralf J. Hosse, Sherif Daouti, Ningping Feng, Kathryn Packman, Huifeng Niu, Valeria Runza, Meher Majety, Barbara Weiser, Claudia Ferrara Koller, Inja Waldhauer, Sandra Grau-Richards, Thomas Friess, Katharina Wartha, and Peter Brünker

Abstract

Figure S1. Related to Figure 1. Characterization of FAP-drozitumab BsAbs and antitumor efficacy in the presence of FAP-expressing fibroblasts in in vitro co-culture models; Table S1. BsAb binding to DR5 and FAP antigens; Table S2. Anti-tumor efficacy of FAP-drozitumab bispecific molecules is FAPdependent.

Published
2023

8. Supplemental Figure 2 from A Novel Carcinoembryonic Antigen T-Cell Bispecific Antibody (CEA TCB) for the Treatment of Solid Tumors

Author

Pablo Umaña, Christian Klein, Vaios Karanikas, Jose Saro, Christiane Jaeger, Thomas von Hirschheydt, Sebastian Neumann, Sherri Dudal, Nathalie Steinhoff, Valeria Nicolini, Mario Perro, Christian Gerdes, Annette Seidl, Teilo Schaller, Sandra Grau-Richards, Peter Bruenker, Oliver Ast, Ekkehard Moessner, Ralf J. Hosse, Thomas Hofer, Steffi Lehmann, Walter Bodmer, Djamila Ouaret, Tina Weinzierl, Sara Colombetti, Johannes Sam, Tanja Fauti, and Marina Bacac

Abstract

Pharmacokinetic profiles of CEA TCB in mice, additional information on CD3 signaling, T cell activation, tumor cell lysis and cytokine release upon CEA TCB and untargeted control TCB treatment.

Published
2023

9. Data from A Novel Carcinoembryonic Antigen T-Cell Bispecific Antibody (CEA TCB) for the Treatment of Solid Tumors

Author

Pablo Umaña, Christian Klein, Vaios Karanikas, Jose Saro, Christiane Jaeger, Thomas von Hirschheydt, Sebastian Neumann, Sherri Dudal, Nathalie Steinhoff, Valeria Nicolini, Mario Perro, Christian Gerdes, Annette Seidl, Teilo Schaller, Sandra Grau-Richards, Peter Bruenker, Oliver Ast, Ekkehard Moessner, Ralf J. Hosse, Thomas Hofer, Steffi Lehmann, Walter Bodmer, Djamila Ouaret, Tina Weinzierl, Sara Colombetti, Johannes Sam, Tanja Fauti, and Marina Bacac

Abstract

Purpose: CEA TCB is a novel IgG-based T-cell bispecific (TCB) antibody for the treatment of CEA-expressing solid tumors currently in phase I clinical trials (NCT02324257). Its format incorporates bivalent binding to CEA, a head-to-tail fusion of CEA- and CD3e-binding Fab domains and an engineered Fc region with completely abolished binding to FcγRs and C1q. The study provides novel mechanistic insights into the activity and mode of action of CEA TCB.Experimental Design: CEA TCB activity was characterized on 110 cell lines in vitro and in xenograft tumor models in vivo using NOG mice engrafted with human peripheral blood mononuclear cells.Results: Simultaneous binding of CEA TCB to tumor and T cells leads to formation of immunologic synapses, T-cell activation, secretion of cytotoxic granules, and tumor cell lysis. CEA TCB activity strongly correlates with CEA expression, with higher potency observed in highly CEA-expressing tumor cells and a threshold of approximately 10,000 CEA-binding sites/cell, which allows distinguishing between high- and low-CEA–expressing tumor and primary epithelial cells, respectively. Genetic factors do not affect CEA TCB activity confirming that CEA expression level is the strongest predictor of CEA TCB activity. In vivo, CEA TCB induces regression of CEA-expressing xenograft tumors with variable amounts of immune cell infiltrate, leads to increased frequency of activated T cells, and converts PD-L1 negative into PD-L1–positive tumors.Conclusions: CEA TCB is a novel generation TCB displaying potent antitumor activity; it is efficacious in poorly infiltrated tumors where it increases T-cell infiltration and generates a highly inflamed tumor microenvironment. Clin Cancer Res; 22(13); 3286–97. ©2016 AACR.

Published
2023

10. Video 2 from A Novel Carcinoembryonic Antigen T-Cell Bispecific Antibody (CEA TCB) for the Treatment of Solid Tumors

Author

Pablo Umaña, Christian Klein, Vaios Karanikas, Jose Saro, Christiane Jaeger, Thomas von Hirschheydt, Sebastian Neumann, Sherri Dudal, Nathalie Steinhoff, Valeria Nicolini, Mario Perro, Christian Gerdes, Annette Seidl, Teilo Schaller, Sandra Grau-Richards, Peter Bruenker, Oliver Ast, Ekkehard Moessner, Ralf J. Hosse, Thomas Hofer, Steffi Lehmann, Walter Bodmer, Djamila Ouaret, Tina Weinzierl, Sara Colombetti, Johannes Sam, Tanja Fauti, and Marina Bacac

Abstract

Representative videos of intravital two-photon (2P) microscopy of tumors treated with CEA TCB. Tumor cells red, T cells green.

Published
2023

11. Video 1 from A Novel Carcinoembryonic Antigen T-Cell Bispecific Antibody (CEA TCB) for the Treatment of Solid Tumors

Author

Pablo Umaña, Christian Klein, Vaios Karanikas, Jose Saro, Christiane Jaeger, Thomas von Hirschheydt, Sebastian Neumann, Sherri Dudal, Nathalie Steinhoff, Valeria Nicolini, Mario Perro, Christian Gerdes, Annette Seidl, Teilo Schaller, Sandra Grau-Richards, Peter Bruenker, Oliver Ast, Ekkehard Moessner, Ralf J. Hosse, Thomas Hofer, Steffi Lehmann, Walter Bodmer, Djamila Ouaret, Tina Weinzierl, Sara Colombetti, Johannes Sam, Tanja Fauti, and Marina Bacac

Abstract

Representative videos of intravital two-photon (2P) microscopy of tumors treated with untargeted TCB. Tumor cells red, T cells green.

Published
2023

12. Table S1 from A Novel Carcinoembryonic Antigen T-Cell Bispecific Antibody (CEA TCB) for the Treatment of Solid Tumors

Author

Pablo Umaña, Christian Klein, Vaios Karanikas, Jose Saro, Christiane Jaeger, Thomas von Hirschheydt, Sebastian Neumann, Sherri Dudal, Nathalie Steinhoff, Valeria Nicolini, Mario Perro, Christian Gerdes, Annette Seidl, Teilo Schaller, Sandra Grau-Richards, Peter Bruenker, Oliver Ast, Ekkehard Moessner, Ralf J. Hosse, Thomas Hofer, Steffi Lehmann, Walter Bodmer, Djamila Ouaret, Tina Weinzierl, Sara Colombetti, Johannes Sam, Tanja Fauti, and Marina Bacac

Abstract

List, Source and CEA binding sites of Cell Lines used in the study

Published
2023

13. Supplemental Figure 1 from A Novel Carcinoembryonic Antigen T-Cell Bispecific Antibody (CEA TCB) for the Treatment of Solid Tumors

Author

Pablo Umaña, Christian Klein, Vaios Karanikas, Jose Saro, Christiane Jaeger, Thomas von Hirschheydt, Sebastian Neumann, Sherri Dudal, Nathalie Steinhoff, Valeria Nicolini, Mario Perro, Christian Gerdes, Annette Seidl, Teilo Schaller, Sandra Grau-Richards, Peter Bruenker, Oliver Ast, Ekkehard Moessner, Ralf J. Hosse, Thomas Hofer, Steffi Lehmann, Walter Bodmer, Djamila Ouaret, Tina Weinzierl, Sara Colombetti, Johannes Sam, Tanja Fauti, and Marina Bacac

Abstract

Assessment of binding of CEA TCB to human and cynomolgus monkey CEA- and CD3-expressing cells, internalization and ADCC, CDC activity.

Published
2023

14. Supplemental Figure 3 from A Novel Carcinoembryonic Antigen T-Cell Bispecific Antibody (CEA TCB) for the Treatment of Solid Tumors

Author

Pablo Umaña, Christian Klein, Vaios Karanikas, Jose Saro, Christiane Jaeger, Thomas von Hirschheydt, Sebastian Neumann, Sherri Dudal, Nathalie Steinhoff, Valeria Nicolini, Mario Perro, Christian Gerdes, Annette Seidl, Teilo Schaller, Sandra Grau-Richards, Peter Bruenker, Oliver Ast, Ekkehard Moessner, Ralf J. Hosse, Thomas Hofer, Steffi Lehmann, Walter Bodmer, Djamila Ouaret, Tina Weinzierl, Sara Colombetti, Johannes Sam, Tanja Fauti, and Marina Bacac

Abstract

Detection of tumor targeting by in vivo imaging (fluorescent intensity, FLI)of CEA TCB formats having bivalent or monovalent binding to CEA and directly labeled with Alexa647.

Published
2023

15. Supplemental Information from A Novel Carcinoembryonic Antigen T-Cell Bispecific Antibody (CEA TCB) for the Treatment of Solid Tumors

Author

Pablo Umaña, Christian Klein, Vaios Karanikas, Jose Saro, Christiane Jaeger, Thomas von Hirschheydt, Sebastian Neumann, Sherri Dudal, Nathalie Steinhoff, Valeria Nicolini, Mario Perro, Christian Gerdes, Annette Seidl, Teilo Schaller, Sandra Grau-Richards, Peter Bruenker, Oliver Ast, Ekkehard Moessner, Ralf J. Hosse, Thomas Hofer, Steffi Lehmann, Walter Bodmer, Djamila Ouaret, Tina Weinzierl, Sara Colombetti, Johannes Sam, Tanja Fauti, and Marina Bacac

Abstract

Supplemental Material and Methods describing CEA TCB production and purification process, determination of affinity and avidity, genetic characterization of cell lines, determination of CEA binding sites, assessment of T cell proliferation and activation, Jurkat NFAT assay, confocal microscopy, FRET, SDPK, in vivo efficacy and imaging studies. Supplemental Video Legends are also within the file.

Published
2023

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