Andreas Lingnau

Cooperative Targeting of Immunotherapy-Resistant Melanoma and Lung Cancer by an AXL-Targeting Antibody–Drug Conjugate and Immune Checkpoint Blockade

Julia Boshuizen, Nora Pencheva, Oscar Krijgsman, Daniela D’Empaire Altimari et autres

Although immune checkpoint blockade (ICB) has shown remarkable clinical benefit in a subset of patients with melanoma and lung cancer, most patients experience no durable benefit. The receptor tyrosine kinase AXL is commonly implicated in therapy resistance and may serve as a …

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Dual Epitope Targeting and Enhanced Hexamerization by DR5 Antibodies as a Novel Approach to Induce Potent Antitumor Activity Through DR5 Agonism

Marije B. Overdijk, Kristin Strumane, Frank J. Beurskens, Antonio Ortiz Buijsse et autres

Abstract Higher-order death receptor 5 (DR5) clustering can induce tumor cell death; however, therapeutic compounds targeting DR5 have achieved limited clinical efficacy. We describe HexaBody-DR5/DR5, an equimolar mixture of two DR5-specific IgG1 antibodies with an Fc-domain mutation that augments antibody hexamerization after …

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Abstract 4544: Multifaceted mechanism of action of DuoHexaBody-CD37 involves both complement- and Fc gamma receptor-mediated cytotoxicity in pre-clinical B-cell lymphoma models

Laurens P. Kil, Simone C. Oostindie, Kristin Strumane, Hilma J. van der Horst et autres

Abstract CD37 is a tetraspanin expressed on mature B cells where it orchestrates plasma membrane organization, receptor signaling, cell migration and adhesion. As CD37 is abundantly expressed on many mature B cell-derived malignancies, it represents an attractive target for new antibody therapies. …

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Abstract C025: HexaBody-DR5/DR5 (GEN1029) shows potent preclinical antitumor activity in a variety of patient-derived xenograft (PDX) tumor models

Marije B. Overdijk, Michael Cecchini, Kristin Strumane, Marcel Brandhorst et autres

Abstract Background: Hyperclustering of death receptor 5 (DR5) and subsequent induction of apoptosis, which normally occurs upon binding of its ligand TRAIL, can be mimicked by agonistic antibodies (Abs). However, clinical efficacy of conventional DR5 Abs has been disappointing. To improve antibody-mediated …

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Hexabody-CD38, a Novel CD38 Antibody with a Hexamerization Enhancing Mutation, Demonstrates Enhanced Complement-Dependent Cytotoxicity and Shows Potent Anti-Tumor Activity in Preclinical Models of Hematological Malignancies

Bart ECG De Goeij, Maarten L. Janmaat, Grietje Andringa, Laurens P. Kil et autres

HexaBody-CD38 (GEN3014) is a novel, hexamerization-enhanced human IgG1 targeting CD38 with superior complement dependent cytotoxicity (CDC) activity, in addition to other effector mechanisms. HexaBody-CD38 carries the E430G mutation and binds a different epitope than the clinically validated CD38 monoclonal antibody daratumumab, which …

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Enapotamab vedotin, an AXL-specific antibody-drug conjugate, shows preclinical antitumor activity in non-small cell lung cancer

Louise A. Koopman, Mikkel G. Terp, Gijs G. Zom, Maarten L. Janmaat et autres

Targeted therapies and immunotherapy have shown promise in patients with non-small cell lung cancer (NSCLC). However, the majority of patients fail or become resistant to treatment, emphasizing the need for novel treatments. In this study, we confirm the prognostic value of levels …

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Abstract 2391: DR5 agonist activity of HexaBody®-DR5/DR5 (GEN1029) is potentiated by C1q and independent of Fc-gamma receptor binding in preclinical tumor models

Marije B. Overdijk, Kristin Strumane, Antonio Ortiz Buijsse, Claudine Vermot‐Desroches et autres

Abstract Hyperclustering of Death Receptor 5 (DR5) after binding of its ligand TRAIL induces apoptosis. Targeting DR5 with agonistic antibodies has been evaluated for the treatment of cancer, however clinical efficacy of conventional DR5-targeting monoclonal antibodies (mAbs) has been disappointing. We applied …

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Targeting hormone refractory prostate cancer by in vivo selected DNA libraries in an orthotopic xenograft mouse model

Laia Civit, Ioanna Théodorou, Franziska Frey, Holger Weber et autres

The targeting of specific tissue is a major challenge for the effective use of therapeutics and agents mediating this targeting are strongly demanded. We report here on an in vivo selection technology that enables the de novo identification of pegylated DNA aptamers …

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C1q potentiates DR5 agonist activity by a mixture of two DR5-specific HexaBody® molecules

Frank J. Beurskens, Marije B. Overdijk, Kristin Strumane, Antonio Ortiz Buijsse et autres

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Abstract 832: An AXL-specific antibody-drug conjugate shows preclinical anti-tumor activity in non-small cell lung cancer, including EGFR-inhibitor resistant NSCLC

Louise A. Koopman, Maarten L. Janmaat, Kirstine Jacobsen, Mikkel G. Terp et autres

Abstract Enhanced AXL expression has been observed in tumor tissues obtained from non-small cell lung (NSCLC) patients, both in drug-treatment naïve patients and in patients with acquired resistance to EGFR tyrosine kinase inhibitors (EGFRi). In this study, we have evaluated the antitumor …

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The impact of donor age, HLA matching and panel reactivity antibodies in pediatric kidney transplant

Beatriz Bañuelos Marco, Therese-Marie Koch, Frank Friedersdorff, Irena Goranova et autres

Abstract 592: Improving therapeutic activity of agonistic DR5 antibodies by inducing target binding-dependent hexamer formation

Marije B. Overdijk, Kristin Strumane, Antonio Ortiz Buijsse, Claudine Vermot‐Desroches et autres

Abstract Death receptor 5 (DR5) is a highly interesting tumor target based on the enhanced sensitivity of cancer cells for DR5-dependent apoptosis. In recent years, multiple therapeutic DR5 antibodies have been evaluated in the clinic for which results however have been disappointing. …

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