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23 results on '"Spitzli, P."'

1. P481: MP0533, A NEW MULTISPECIFIC DARPIN CD3 ENGAGER TARGETING THREE TUMOR ASSOCIATED ANTIGENS, INDUCES SPECIFIC T-CELL ACTIVATION AND AML TUMOR KILLING IN VIVO

Author

A. Croset, M. Bianchi, M. Franchini, T. Lekishvili, Y. Kaufmann, A. Auge, M. Hänggi, W. Ali, C. Zitt, S. Wullschleger, M. Matzner, C. Reichen, S. Fischer, Y. Grübler, A. Eggenschwiler, T. Looser, R. Watson, P. Spitzli, V. Kirkin, D. Steiner, and A. Goubier

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Published
2022
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2. P481: MP0533, A NEW MULTISPECIFIC DARPIN CD3 ENGAGER TARGETING THREE TUMOR ASSOCIATED ANTIGENS, INDUCES SPECIFIC T-CELL ACTIVATION AND AML TUMOR KILLING IN VIVO

Author

Croset, A., primary, Bianchi, M., additional, Franchini, M., additional, Lekishvili, T., additional, Kaufmann, Y., additional, Auge, A., additional, Hänggi, M., additional, Ali, W., additional, Zitt, C., additional, Wullschleger, S., additional, Matzner, M., additional, Reichen, C., additional, Fischer, S., additional, Grübler, Y., additional, Eggenschwiler, A., additional, Looser, T., additional, Watson, R., additional, Spitzli, P., additional, Kirkin, V., additional, Steiner, D., additional, and Goubier, A., additional

Published
2022
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6. MP0533: A Multispecific Darpin CD3 Engager Targeting CD33, CD123, and CD70 for the Treatment of AML and MDS Designed to Selectively Target Leukemic Stem Cells

Author

Bianchi, Matteo, Reichen, Christian, Fischer, Stefanie, Grübler, Yvonne, Eggenschwiler, Aline, Marpakwar, Rajlakshmi, Looser, Thamar, Spitzli, Patricia, Herzog, Christel, Villemagne, Denis, Kaufmann, Yvonne, Auge, Alienor, Hänggi, Martin, Ali, Waleed, Lekishvili, Tamara, Frasconi, Teresa, Wullschleger, Stephan, Zitt, Christof, Franchini, Marco, Croset, Amelie, Watson, Randall, Kirkin, Vladimir, Luethi, Ursina, Ochsenbein, Adrian, Riether, Carsten, Steiner, Daniel, Leupin, Nicolas, and Goubier, Anne

Published
2022
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7. Avidity-Engineered CD3 Engaging DARPin ® Targeting Three Tumor Associated Antigens Induce Strong and Specific T Cell Dependent Killing of AML Cells with Potential for Improved Safety

Author

Bianchi, Matteo, Reschke, Nina, Reichen, Christian, Fischer, Stefanie, Grübler, Yvonne, Eggenschwiler, Aline, Krieg, Jennifer, Ioannou, Kyriaki, Ragusa, Simone, Looser, Thamar, Spitzli, Patricia, Herzog, Christel, Villemagne, Denis, Kaufmann, Yvonne, Matzner, Mirela, Auge, Alienor, Hänggi, Martin, Ali, Waleed, Franchini, Marco, Kirkin, Vladimir, Schlereth, Bernd, Luethi, Ursina, Ochsenbein, Adrian, Riether, Carsten, Steiner, Daniel, and Goubier, Anne

Abstract

AML is driven by leukemic stem cells (LSC) that resist conventional chemotherapies and remain unaffected in their niche, continually replenishing circulating blast cells. We postulated that an avidity-engineered CD3 engaging DARPin ® (Designed Ankyrin Repeat Protein) able to simultaneously target LSC-specific CD70 as well as CD123 and CD33 could allow highly efficient and specific T cell-mediated killing of AML LSCs and circulating blast cells while preserving a therapeutic window towards healthy cells. Moreover, this simultaneous targeting of three different tumor associated antigens (TAAs) has the potential to address tumor heterogeneity, allowing targeting of AML cells with different co-expression patterns and/or expression levels of each single TAA. To achieve this ambitious goal we used our DARPin ® platform to build a novel class of triple targeting CD3 engaging molecules.

Published
2021
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8. Magnetic susceptibility of (rare earth)xMo6S8

Author

Pelizzone, M., Treyvaud, A., Spitzli, P., and Fischer, Ø.

Abstract

We have studied the susceptibility of all (RE)xMo6S8 compounds between 1.3 and 300 K (RE = rare earth). In the two superconducting compounds Ho1.2Mo6S8 and Dy1.2Mo6S8 magnetic ordering is expected in the temperature range 0.1–1 K. The magnetic transition in CeMo6S8 at2.25 K is of antiferromagnetic nature. A second anomaly at 1.6 K in this compound may announce a low-temperature ferromagnetic state.

Published
1977
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23. The CD33xCD123xCD70 Multispecific CD3-Engaging DARPin MP0533 Induces Selective T Cell-Mediated Killing of AML Leukemic Stem Cells.

Author

Bianchi M, Reichen C, Croset A, Fischer S, Eggenschwiler A, Grübler Y, Marpakwar R, Looser T, Spitzli P, Herzog C, Villemagne D, Schiegg D, Abduli L, Iss C, Neculcea A, Franchini M, Lekishvili T, Ragusa S, Zitt C, Kaufmann Y, Auge A, Hänggi M, Ali W, Frasconi TM, Wullschleger S, Schlegel I, Matzner M, Lüthi U, Schlereth B, Dawson KM, Kirkin V, Ochsenbein AF, Grimm S, Reschke N, Riether C, Steiner D, Leupin N, and Goubier A

Subjects
Humans, Animals, Mice, Interleukin-3 Receptor alpha Subunit immunology, Interleukin-3 Receptor alpha Subunit metabolism, Xenograft Model Antitumor Assays, Sialic Acid Binding Ig-like Lectin 3 metabolism, Sialic Acid Binding Ig-like Lectin 3 immunology, CD3 Complex immunology, Cell Line, Tumor, Cytotoxicity, Immunologic, Leukemia, Myeloid, Acute immunology, Leukemia, Myeloid, Acute therapy, Leukemia, Myeloid, Acute pathology, Neoplastic Stem Cells immunology, Neoplastic Stem Cells metabolism, T-Lymphocytes immunology, T-Lymphocytes metabolism
Abstract

The prognosis of patients with acute myeloid leukemia (AML) is limited, especially for elderly or unfit patients not eligible for hematopoietic stem cell (HSC) transplantation. The disease is driven by leukemic stem cells (LSCs), which are characterized by clonal heterogeneity and resistance to conventional therapy. These cells are therefore believed to be a major cause of progression and relapse. We designed MP0533, a multispecific CD3-engaging designed ankyrin repeat protein (DARPin) that can simultaneously bind to three antigens on AML cells (CD33, CD123, and CD70), aiming to enable avidity-driven T cell-mediated killing of AML cells coexpressing at least two of the antigens. In vitro, MP0533 induced selective T cell-mediated killing of AML cell lines, as well as patient-derived AML blasts and LSCs, expressing two or more target antigens, while sparing healthy HSCs, blood, and endothelial cells. The higher selectivity also resulted in markedly lower levels of cytokine release in normal human blood compared to single antigen-targeting T-cell engagers. In xenograft AML mice models, MP0533 induced tumor-localized T-cell activation and cytokine release, leading to complete eradication of the tumors while having no systemic adverse effects. These studies show that the multispecific-targeting strategy used with MP0533 holds promise for improved selectivity toward LSCs and efficacy against clonal heterogeneity, potentially bringing a new therapeutic option to this group of patients with a high unmet need. MP0533 is currently being evaluated in a dose-escalation phase 1 study in patients with relapsed or refractory AML (NCT05673057)., (©2024 The Authors; Published by the American Association for Cancer Research.)

Published
2024
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