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An Attenuated Targeted-TNF Localizes to Tumors In Vivo and Regains Activity at the Site of Disease.
Int J Mol Sci
September 2021
Philochem AG, CH-8112 Otelfingen, Switzerland.
Antibody-cytokine fusion proteins (immunocytokines) are gaining importance for cancer therapy, but those products are often limited by systemic toxicity related to the activity of the cytokine payload in circulation and in secondary lymphoid organs. Tumor necrosis factor (TNF) is used as a pro-inflammatory payload to trigger haemorrhagic necrosis and boost anti-cancer immunity at the tumor site. Here we describe a depotentiated version of TNF (carrying the single point mutation I97A), which displayed reduced binding affinity to its cognate receptor tumor necrosis factor receptor 1 (TNFR-1) and lower biocidal activity.
View Article and Find Full Text PDFCancer therapy in mice using a pure population of CD8 T cell specific to the AH1 tumor rejection antigen.
Cancer Immunol Immunother
November 2021
Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH Zürich), Vladimir-Prelog-Weg 4, 8093, Zurich, Switzerland.
There is a growing interest in the use of patient-derived T cells for the treatment of various types of malignancies. The expansion of a polyclonal and polyspecific population of tumor-reactive T cells, with a subsequent infusion into the same donor patient, has been implemented, sometimes with positive results. It is not known, however, whether a set of T cells with a single antigen specificity may be sufficient for an effective therapy.
View Article and Find Full Text PDFImmunotherapy of CT26 murine tumors is characterized by an oligoclonal response of tissue-resident memory T cells against the AH1 rejection antigen.
Eur J Immunol
October 2020
Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH Zürich), Zürich, Switzerland.
Mice bearing CT26 tumors can be cured by administration of L19-mIL12 or F8-mTNF, two antibody fusion proteins which selectively deliver their cytokine payload to the tumor. In both settings, cancer cures crucially depended on CD8 T cells and the AH1 peptide (derived from the gp70 protein of the murine leukemia virus) acted as the main tumor-rejection antigen, with ∼50% of CD8 T cells in the neoplastic mass being AH1-specific after therapy. In order to characterize the clonality of the T cell response, its phenotype, and activation status, we isolated CD8 T cells from tumors and secondary lymphoid organs and submitted them to T cell receptor (TCR) and total mRNA sequencing.
View Article and Find Full Text PDFAntibody-based delivery of interleukin-2 to neovasculature has potent activity against acute myeloid leukemia.
Sci Transl Med
September 2013
Department of Chemistry and Applied Biosciences, ETH Zürich, Wolfgang-Pauli-Strasse 10, CH-8093 Zurich, Switzerland.
Acute myeloid leukemia (AML) is a rapidly progressing disease that is accompanied by a strong increase in microvessel density in the bone marrow. This observation prompted us to stain biopsies of AML and acute lymphoid leukemia (ALL) patients with the clinical-stage human monoclonal antibodies F8, L19, and F16 directed against markers of tumor angiogenesis. The analysis revealed that the F8 and F16 antibodies strongly stained 70% of AML and 75% of ALL bone marrow specimens, whereas chloroma biopsies were stained with all three antibodies.
View Article and Find Full Text PDFL19. Lymphoid neogenesis in vascular chronic inflammation.
Presse Med
April 2013
Unité 698, institut national de la santé et de la recherche médicale, hôpital Xavier-Bichat, Inserm UMRS698, GH Bichat-Claude Bernard, université Denis-Diderot, 46, rue Henri-Huchard, 75877 Paris cedex 18, France.
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