Carmel M. Lynch

Molecular epidemiology of the expression of urokinase plasminogen activator receptor-associated protein (uPARAP) in mesenchymal malignancies

Chao-Chi Wang, Pernille Barkholt, Agnieszka Woźniak, Ulla Vanleeuw et autres

• uPARAP expression was assessed in sarcoma samples and normal tissues using tissue microarrays. • High uPARAP expression was observed in the majority of sarcoma subtypes analyzed. • uPARAP showed limited expression in normal tissues. • Most sarcoma subtypes did not show …

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Abstract 4784: ADCE-D01: a first in class antibody drug conjugate against urokinase plasminogen activator receptor-associated protein (uPARAP) demonstrates excellent preclinical efficacy and tolerability

Jonathan Henry Wardman, Anne Sigaard Bie, Christophé Côme, Pernille Barkholt et autres

Abstract The urokinase plasminogen activator receptor-associated protein (uPARAP, endo180, CD280) is a type-1 membrane protein which acts as an endocytic receptor for collagen. uPARAP binds and internalizes both intact and partially degraded collagens. uPARAP-bound collagen is internalized via clathrin-mediated endocytosis and routed …

Abstract 5597: Efficacy of novel urokinase plasminogen activator receptor-associated protein targeted antibody-drug conjugates in patient-derived xenografts of soft tissue sarcoma

Chao‐Chi Wang, Agnieszka Woźniak, Luna De Sutter, Lore De Cock et autres

Abstract Objective: Soft tissue sarcoma is a heterogeneous group of rare malignant tumors with a high unmet medical need. We evaluated the efficacy of two novel antibody-drug conjugates (ADC), ADCE-017 and ADCE-202, each consisting of three components: (1) an antibody targeting urokinase …

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Abstract 6355: Urokinase plasminogen activator receptor-associated protein (uPARAP) is overexpressed in human glioblastomas and is a therapeutic target for antibody-drug conjugates (ADC)

Ida Gregersen, C Løkke, Jette B. Lange, Pernille Barkholt et autres

Abstract Background: Glioblastoma Multiforme (GBM), primarily arising in the brain's frontal and temporal lobes, is a devastating malignancy originating from astrocytes. Despite treatment advancements, the prognosis remains bleak, with a median survival of 15-18 months and a 10% five-year survival rate.Our study …

Abstract 1547: The urokinase plasminogen activator receptor-associated protein (uPARAP) is an attractive target for the development of antibody-drug conjugates (ADCs) for treatment of mesenchymal malignancies

Pernille Barkholt, Agnieszka Woźniak, Chao‐Chi Wang, Che‐Jui Lee et autres

Abstract Background: Soft tissue sarcoma (STS) is a complex family of rare malignancies with high unmet medical need. uPARAP is an endocytic receptor expressed at low levels on selected mesenchymal cell types, which internalizes fragments of collagen and transfers them to the …

Data from MEN1309/OBT076, a First-In-Class Antibody–Drug Conjugate Targeting CD205 in Solid Tumors

Giuseppe Merlino, Alessio Fiascarelli, Mario Bigioni, Alessandro Bressan et autres

Abstract CD205 is a type I transmembrane glycoprotein and is a member of the C-type lectin receptor family. Analysis by mass spectrometry revealed that CD205 was robustly expressed and highly prevalent in a variety of solid malignancies from different histotypes. IHC confirmed …

Supplementary Data from MEN1309/OBT076, a First-In-Class Antibody–Drug Conjugate Targeting CD205 in Solid Tumors

Giuseppe Merlino, Alessio Fiascarelli, Mario Bigioni, Alessandro Bressan et autres

Supplementary Materials and Methods

Supplementary Figure S1 from MEN1309/OBT076, a First-In-Class Antibody–Drug Conjugate Targeting CD205 in Solid Tumors

Giuseppe Merlino, Alessio Fiascarelli, Mario Bigioni, Alessandro Bressan et autres

Supplementary Figure S1. Representative images of IHC staining for CD205 in different human and cynomolgus tissues, obtained with 2 μg/ml of MEN1309/OBT076 at 20X and 10X magnification. 1) Human donor spleen; moderate to strong membranous/granular cytoplasmic staining of several mononuclear cells present …

Supplementary Figure S2 from MEN1309/OBT076, a First-In-Class Antibody–Drug Conjugate Targeting CD205 in Solid Tumors

Giuseppe Merlino, Alessio Fiascarelli, Mario Bigioni, Alessandro Bressan et autres

Supplementary Figure S2. In vitro characterization of MEN1309/OBT076. A) ELISA assay showed that both the unconjugated and DM4-conjugated antibodies were able to bind FcγRIIIA with the same affinity (n=2). B) FACS binding experiment on THP-1 cell line, performed by titrating unlabeled antibody …

Supplementary Table S3 from MEN1309/OBT076, a First-In-Class Antibody–Drug Conjugate Targeting CD205 in Solid Tumors

Giuseppe Merlino, Alessio Fiascarelli, Mario Bigioni, Alessandro Bressan et autres

Supplementary Table S3: Cross reactivity data obtained from whole blood of different species. Values are expressed as the concentration at which MBH1309/OBT076 has half-maximum binding [EC50].

Supplementary S3 A-B from MEN1309/OBT076, a First-In-Class Antibody–Drug Conjugate Targeting CD205 in Solid Tumors

Giuseppe Merlino, Alessio Fiascarelli, Mario Bigioni, Alessandro Bressan et autres

Supplementary Figure S3-A. Representative image of IHC staining for CD205 in a tumor mass from HCC-70 xenograft model, 16 days far from the initial treatment with 5 mg/kg of MEN1309/OBT076. The semiquantitative IHC analysis showed a score of 1+ in 30% of …

Supplementary Tables S1-S2 from MEN1309/OBT076, a First-In-Class Antibody–Drug Conjugate Targeting CD205 in Solid Tumors

Giuseppe Merlino, Alessio Fiascarelli, Mario Bigioni, Alessandro Bressan et autres

Supplementary Table S1. Commercial tumor TMAs representing different solid tumor types. Supplementary Table S2. Summary of CD205 expression in human solid tumor types.