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Research paper thumbnail of A Novel Functional Polymorphism in the<i>Transforming Growth Factor-β2</i>Gene Promoter and Tumor Progression in Breast Cancer

Cancer Research, Aug 1, 2006

Research paper thumbnail of Supplementary Figure Legend from Tetravalent Antibody–scTRAIL Fusion Proteins with Improved Properties

Research paper thumbnail of Supplementary Figure 2 from Tetravalent Antibody–scTRAIL Fusion Proteins with Improved Properties

Research paper thumbnail of Supplementary Figure S5 from Superior Properties of Fc-comprising scTRAIL Fusion Proteins

Research paper thumbnail of The extracellular domains of FasL and Fas are sufficient for the formation of supramolecular FasL-Fas clusters of high stability

Journal of Cell Biology, Mar 28, 2005

Research paper thumbnail of Supplementary Figure S1 from Superior Properties of Fc-comprising scTRAIL Fusion Proteins

Research paper thumbnail of Supplementary Figure S4 from Superior Properties of Fc-comprising scTRAIL Fusion Proteins

Figure S4 provides data on a comparison of bioactivity of dimeric EHD2-scTRAIL and the high molec... more Figure S4 provides data on a comparison of bioactivity of dimeric EHD2-scTRAIL and the high molecular weight fraction.

Research paper thumbnail of Supplementary Figure 1 from Antiestrogens Induce Transforming Growth Factor β–Mediated Immunosuppression in Breast Cancer

Supplementary Figure 1 from Antiestrogens Induce Transforming Growth Factor β–Mediated Immunosupp... more Supplementary Figure 1 from Antiestrogens Induce Transforming Growth Factor β–Mediated Immunosuppression in Breast Cancer

Research paper thumbnail of Novel TRAIL variants for targeted cancer therapy

Journal of Clinical Oncology, 2010

e13592 Background: Targeting the apoptotic machinery of malignant cells is one attractive concept... more e13592 Background: Targeting the apoptotic machinery of malignant cells is one attractive concept for the treatment of cancer, which is currently exploited for TRAIL at various stages of preclinica...

Research paper thumbnail of TNFR80-Dependent Enhancement of TNFR60-Induced Cell Death Is Mediated by TNFR-Associated Factor 2 and Is Specific for TNFR60

The Journal of Immunology

Costimulation of TNFR80 can strongly enhance TNFR60-induced cell death. In this study, we show th... more Costimulation of TNFR80 can strongly enhance TNFR60-induced cell death. In this study, we show that this enhancement is TNFR60 selective, as neither TNF-related apoptosis-inducing ligand/Apo2 ligand-, Apo1/Fas-, ceramide-, nor daunorubicin-mediated cell death was affected by costimulation of TNFR80. We further demonstrate that TNFR-associated factor 2 (TRAF2) is critically involved in both negative and positive regulation of TNF-induced cell death. Overexpression of TRAF2 and of a TRAF2 mutant, deficient in nuclear factor-κB activation, selectively desensitized and enhanced, respectively, TNFR60-induced cell death in HeLa cells. However, upon costimulation of TNFR80, which mediates activation of nuclear factor-κB and the c-Jun amino-terminal kinase via TRAF2, TNF-induced cell death is drastically enhanced in parental and TRAF2-transfected, but not in TRAF2 (87–501)-transfected cells. These data point to a critical role of TRAF2 in the apoptotic TNFR cross talk, whereby the TNFR80-de...

Research paper thumbnail of Supplementary Figure S3 from Superior Properties of Fc-comprising scTRAIL Fusion Proteins

Figure S3 provides data on cell death induction of scTRAIL fusion proteins

Research paper thumbnail of Supplementary Figure S2 from Superior Properties of Fc-comprising scTRAIL Fusion Proteins

Figure S2 provides data on target binding of scTRAIL molecules in ELISA

Research paper thumbnail of Supplementary Figure S7 from Superior Properties of Fc-comprising scTRAIL Fusion Proteins

Figure S7 provides data on safety of the treatments with EGFR-targeted scTRAIL fusion proteins an... more Figure S7 provides data on safety of the treatments with EGFR-targeted scTRAIL fusion proteins and Fc-scTRAIL in combination with bortezomib.

Research paper thumbnail of Supplementary Figure 6 from Superior Properties of Fc-comprising scTRAIL Fusion Proteins

Figure S6 provides data on biochemical and functional characterization of Fc-scTRAIL8M.

Research paper thumbnail of Supplementary Figure 3 from Tetravalent Antibody–scTRAIL Fusion Proteins with Improved Properties

PDF file - 110K, Supplementary Figure 3. In vitro cytotoxicity of scFv-EHD2-scTRAIL in comparison... more PDF file - 110K, Supplementary Figure 3. In vitro cytotoxicity of scFv-EHD2-scTRAIL in comparison with Db-scTRAIL.

Research paper thumbnail of Supplementary Figure 1 from Tetravalent Antibody–scTRAIL Fusion Proteins with Improved Properties

PDF file - 132K, Supplementary Figure 1. Determination of melting points of the different fusion ... more PDF file - 132K, Supplementary Figure 1. Determination of melting points of the different fusion proteins by dynamic light scattering.

Research paper thumbnail of Supplementary Tables 1 - 2 from Tetravalent Antibody–scTRAIL Fusion Proteins with Improved Properties

PDF file - 85K, Supplementary Table 1: In vitro cytotoxicity; Supplementary Table 2: Pharmacokine... more PDF file - 85K, Supplementary Table 1: In vitro cytotoxicity; Supplementary Table 2: Pharmacokinetic properties of EHD2 fusion proteins

Research paper thumbnail of Supplementary Figures from OMTX705, a Novel FAP-Targeting ADC Demonstrates Activity in Chemotherapy and Pembrolizumab-Resistant Solid Tumor Models

S1-S7 all supplementary figures with their legends: S1:Figure S1. OMTX705 binding and internaliza... more S1-S7 all supplementary figures with their legends: S1:Figure S1. OMTX705 binding and internalization in HT1080-WT, -FAP and CAFs S2:Weight change of mice bearing Panc 007, Lung 024 and Breast 014 tumors. S3: OMTX705 Activity in the Immunodeficient Patient Derived Xenografts (PDX) Models of Ovarian Cancer. S4: FAP immunostaining in frozen tumor samples from humanized mice bearing CTG-0860 NSCLC PDX tumor. S5: Separate fluorescent staining of human IgG, Rab7 and nuclei in OMTX705 and OMTX005 treated HT1080-FAP cells (complements the merged image of figure 4C) S6: Immunohistochemical analysis of payload, OMTX005 and OMTX705 distribution in tumors from Panc 007 model. S7: Schematic summary of findings and proposed mechanism of action of OMTX705.

Research paper thumbnail of Supplementary Materials and Methods from OMTX705, a Novel FAP-Targeting ADC Demonstrates Activity in Chemotherapy and Pembrolizumab-Resistant Solid Tumor Models

Additional Materials and Methods information not included in the article text, and detailed descr... more Additional Materials and Methods information not included in the article text, and detailed description of the patient tumors from which xenograft models have been derived from

Research paper thumbnail of Data from OMTX705, a Novel FAP-Targeting ADC Demonstrates Activity in Chemotherapy and Pembrolizumab-Resistant Solid Tumor Models

Purpose:The tumor microenvironment plays a key role in cancer development and progression and is ... more Purpose:The tumor microenvironment plays a key role in cancer development and progression and is involved in resistance to chemo- and immunotherapy. Cancer-associated fibroblast expressing fibroblast-activating protein α (FAPα) is one of the predominant stroma cell types and is involved in resistance to immunotherapy.Experimental Design:We generated OMTX705, a novel antibody–drug conjugate from a humanized anti-FAP antibody linked to a new cytolysin. Here, we studied its antineoplastic activity in vitro and in preclinical mouse models alone and in combination with chemotherapy as well as immunotherapy in PD-1–resistant tumors.Results:In Avatar models, OMTX705 showed a 100% tumor growth inhibition and prolonged tumor regressions as single agent and in combination with chemotherapy. Treatment rechallenge following treatment discontinuation induced additional tumor regression, suggesting lack of treatment resistance. In a mouse model with a humanized immune system resistant to PD-1 inh...

Research paper thumbnail of A Novel Functional Polymorphism in the<i>Transforming Growth Factor-β2</i>Gene Promoter and Tumor Progression in Breast Cancer

Cancer Research, Aug 1, 2006

Research paper thumbnail of Supplementary Figure Legend from Tetravalent Antibody–scTRAIL Fusion Proteins with Improved Properties

Research paper thumbnail of Supplementary Figure 2 from Tetravalent Antibody–scTRAIL Fusion Proteins with Improved Properties

Research paper thumbnail of Supplementary Figure S5 from Superior Properties of Fc-comprising scTRAIL Fusion Proteins

Research paper thumbnail of The extracellular domains of FasL and Fas are sufficient for the formation of supramolecular FasL-Fas clusters of high stability

Journal of Cell Biology, Mar 28, 2005

Research paper thumbnail of Supplementary Figure S1 from Superior Properties of Fc-comprising scTRAIL Fusion Proteins

Research paper thumbnail of Supplementary Figure S4 from Superior Properties of Fc-comprising scTRAIL Fusion Proteins

Figure S4 provides data on a comparison of bioactivity of dimeric EHD2-scTRAIL and the high molec... more Figure S4 provides data on a comparison of bioactivity of dimeric EHD2-scTRAIL and the high molecular weight fraction.

Research paper thumbnail of Supplementary Figure 1 from Antiestrogens Induce Transforming Growth Factor β–Mediated Immunosuppression in Breast Cancer

Supplementary Figure 1 from Antiestrogens Induce Transforming Growth Factor β–Mediated Immunosupp... more Supplementary Figure 1 from Antiestrogens Induce Transforming Growth Factor β–Mediated Immunosuppression in Breast Cancer

Research paper thumbnail of Novel TRAIL variants for targeted cancer therapy

Journal of Clinical Oncology, 2010

e13592 Background: Targeting the apoptotic machinery of malignant cells is one attractive concept... more e13592 Background: Targeting the apoptotic machinery of malignant cells is one attractive concept for the treatment of cancer, which is currently exploited for TRAIL at various stages of preclinica...

Research paper thumbnail of TNFR80-Dependent Enhancement of TNFR60-Induced Cell Death Is Mediated by TNFR-Associated Factor 2 and Is Specific for TNFR60

The Journal of Immunology

Costimulation of TNFR80 can strongly enhance TNFR60-induced cell death. In this study, we show th... more Costimulation of TNFR80 can strongly enhance TNFR60-induced cell death. In this study, we show that this enhancement is TNFR60 selective, as neither TNF-related apoptosis-inducing ligand/Apo2 ligand-, Apo1/Fas-, ceramide-, nor daunorubicin-mediated cell death was affected by costimulation of TNFR80. We further demonstrate that TNFR-associated factor 2 (TRAF2) is critically involved in both negative and positive regulation of TNF-induced cell death. Overexpression of TRAF2 and of a TRAF2 mutant, deficient in nuclear factor-κB activation, selectively desensitized and enhanced, respectively, TNFR60-induced cell death in HeLa cells. However, upon costimulation of TNFR80, which mediates activation of nuclear factor-κB and the c-Jun amino-terminal kinase via TRAF2, TNF-induced cell death is drastically enhanced in parental and TRAF2-transfected, but not in TRAF2 (87–501)-transfected cells. These data point to a critical role of TRAF2 in the apoptotic TNFR cross talk, whereby the TNFR80-de...

Research paper thumbnail of Supplementary Figure S3 from Superior Properties of Fc-comprising scTRAIL Fusion Proteins

Figure S3 provides data on cell death induction of scTRAIL fusion proteins

Research paper thumbnail of Supplementary Figure S2 from Superior Properties of Fc-comprising scTRAIL Fusion Proteins

Figure S2 provides data on target binding of scTRAIL molecules in ELISA

Research paper thumbnail of Supplementary Figure S7 from Superior Properties of Fc-comprising scTRAIL Fusion Proteins

Figure S7 provides data on safety of the treatments with EGFR-targeted scTRAIL fusion proteins an... more Figure S7 provides data on safety of the treatments with EGFR-targeted scTRAIL fusion proteins and Fc-scTRAIL in combination with bortezomib.

Research paper thumbnail of Supplementary Figure 6 from Superior Properties of Fc-comprising scTRAIL Fusion Proteins

Figure S6 provides data on biochemical and functional characterization of Fc-scTRAIL8M.

Research paper thumbnail of Supplementary Figure 3 from Tetravalent Antibody–scTRAIL Fusion Proteins with Improved Properties

PDF file - 110K, Supplementary Figure 3. In vitro cytotoxicity of scFv-EHD2-scTRAIL in comparison... more PDF file - 110K, Supplementary Figure 3. In vitro cytotoxicity of scFv-EHD2-scTRAIL in comparison with Db-scTRAIL.

Research paper thumbnail of Supplementary Figure 1 from Tetravalent Antibody–scTRAIL Fusion Proteins with Improved Properties

PDF file - 132K, Supplementary Figure 1. Determination of melting points of the different fusion ... more PDF file - 132K, Supplementary Figure 1. Determination of melting points of the different fusion proteins by dynamic light scattering.

Research paper thumbnail of Supplementary Tables 1 - 2 from Tetravalent Antibody–scTRAIL Fusion Proteins with Improved Properties

PDF file - 85K, Supplementary Table 1: In vitro cytotoxicity; Supplementary Table 2: Pharmacokine... more PDF file - 85K, Supplementary Table 1: In vitro cytotoxicity; Supplementary Table 2: Pharmacokinetic properties of EHD2 fusion proteins

Research paper thumbnail of Supplementary Figures from OMTX705, a Novel FAP-Targeting ADC Demonstrates Activity in Chemotherapy and Pembrolizumab-Resistant Solid Tumor Models

S1-S7 all supplementary figures with their legends: S1:Figure S1. OMTX705 binding and internaliza... more S1-S7 all supplementary figures with their legends: S1:Figure S1. OMTX705 binding and internalization in HT1080-WT, -FAP and CAFs S2:Weight change of mice bearing Panc 007, Lung 024 and Breast 014 tumors. S3: OMTX705 Activity in the Immunodeficient Patient Derived Xenografts (PDX) Models of Ovarian Cancer. S4: FAP immunostaining in frozen tumor samples from humanized mice bearing CTG-0860 NSCLC PDX tumor. S5: Separate fluorescent staining of human IgG, Rab7 and nuclei in OMTX705 and OMTX005 treated HT1080-FAP cells (complements the merged image of figure 4C) S6: Immunohistochemical analysis of payload, OMTX005 and OMTX705 distribution in tumors from Panc 007 model. S7: Schematic summary of findings and proposed mechanism of action of OMTX705.

Research paper thumbnail of Supplementary Materials and Methods from OMTX705, a Novel FAP-Targeting ADC Demonstrates Activity in Chemotherapy and Pembrolizumab-Resistant Solid Tumor Models

Additional Materials and Methods information not included in the article text, and detailed descr... more Additional Materials and Methods information not included in the article text, and detailed description of the patient tumors from which xenograft models have been derived from

Research paper thumbnail of Data from OMTX705, a Novel FAP-Targeting ADC Demonstrates Activity in Chemotherapy and Pembrolizumab-Resistant Solid Tumor Models

Purpose:The tumor microenvironment plays a key role in cancer development and progression and is ... more Purpose:The tumor microenvironment plays a key role in cancer development and progression and is involved in resistance to chemo- and immunotherapy. Cancer-associated fibroblast expressing fibroblast-activating protein α (FAPα) is one of the predominant stroma cell types and is involved in resistance to immunotherapy.Experimental Design:We generated OMTX705, a novel antibody–drug conjugate from a humanized anti-FAP antibody linked to a new cytolysin. Here, we studied its antineoplastic activity in vitro and in preclinical mouse models alone and in combination with chemotherapy as well as immunotherapy in PD-1–resistant tumors.Results:In Avatar models, OMTX705 showed a 100% tumor growth inhibition and prolonged tumor regressions as single agent and in combination with chemotherapy. Treatment rechallenge following treatment discontinuation induced additional tumor regression, suggesting lack of treatment resistance. In a mouse model with a humanized immune system resistant to PD-1 inh...