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The immunocytokine L19-TNF eradicates Sarcomas in combination with Chemotherapy agents or with immune check-point inhibitors

View ORCID ProfileRiccardo Corbellari, View ORCID ProfileLisa Nadal, View ORCID ProfileAlessandra Villa, View ORCID ProfileDario Neri, View ORCID ProfileRoberto De Luca
doi: https://doi.org/10.1101/830406
Riccardo Corbellari
1University of Trento, Italy, CiBIO (Department of Cellular, Computational and Integrative Biology), Via Sommarive 9, 38123 Povo (Trento)
2Philochem AG, Otelfingen, Switzerland
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Lisa Nadal
1University of Trento, Italy, CiBIO (Department of Cellular, Computational and Integrative Biology), Via Sommarive 9, 38123 Povo (Trento)
2Philochem AG, Otelfingen, Switzerland
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Alessandra Villa
2Philochem AG, Otelfingen, Switzerland
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Dario Neri
3Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH Zürich), Zurich, Switzerland
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Roberto De Luca
2Philochem AG, Otelfingen, Switzerland
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  • For correspondence: roberto.deluca@philogen.com
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Abstract

Antibody-cytokine fusion proteins (also called “immunocytokines”) represent an emerging class of biopharmaceutical products, which are being considered for cancer immunotherapy. When used as single agents, pro-inflammatory immunocytokines are rarely capable of induce complete and durable cancer regression in mouse models and in patients. However, the combination treatment with conventional chemotherapy or with other immune-stimulatory agents typically increases the therapeutic efficacy of immunocytokines.

In this article, we describe combination treatments of a tumor-targeting antibody-cytokine fusion protein based on the L19 antibody (specific to a splice isoform of fibronectin) fused to murine tumor necrosis factor (TNF) with standard chemotherapy (dacarbazine, trabectedin or melphalan) or with an immune check-point inhibitor (anti-PD-1) in a BALB/c derived immunocompetent murine model of sarcoma (WEHI-164).

All combination treatments led to improved tumor remission compared to single agent treatments, suggesting that these combination partners may be suitable for further clinical development in sarcoma patients.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted February 04, 2020.
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The immunocytokine L19-TNF eradicates Sarcomas in combination with Chemotherapy agents or with immune check-point inhibitors
Riccardo Corbellari, Lisa Nadal, Alessandra Villa, Dario Neri, Roberto De Luca
bioRxiv 830406; doi: https://doi.org/10.1101/830406
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The immunocytokine L19-TNF eradicates Sarcomas in combination with Chemotherapy agents or with immune check-point inhibitors
Riccardo Corbellari, Lisa Nadal, Alessandra Villa, Dario Neri, Roberto De Luca
bioRxiv 830406; doi: https://doi.org/10.1101/830406

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