du145 psma cell line  (Novartis)

Journal: Cancer research

Article Title: Increased Tumor Penetration of Single-Domain Antibody Drug Conjugates Improves In Vivo Efficacy in Prostate Cancer Models

doi: 10.1158/0008-5472.CAN-19-2295

Figure Lengend Snippet: The ADCs were used in two separate tumor inhibition studies involving nude mice with either a high expression DU145-PSMA xenograft (A) or a moderate expressing CWR22Rv1 xenograft (B). The table displays relative internalization and clearance rates alongside ADC structures (all conjugations occurred at the C-terminus) and the in vitro potencies (C). The IC50 for monovalent and biparatopic antibody conjugates with and without an albumin binding ‘Half-Life Extension’ (HLE) were determined in DU145-PSMA cells. *VH2-VH1-DGN549 was dosed every other day for three total doses at a 10μg/kg DGN549 per dose for the CWR22Rv1 study and as a single bolus dose of 30 μg/kg DGN5459 in the DU145-PSMA study. Slashes mark mice removed early from the study (see Supplementary Methods).

Article Snippet: Cell Culture and Animals The DU145 cell line (RRID: CVCL_0105, PSMA negative, certified by ATCC via STR analysis) and PSMA transfected DU145 cell line generated by Kampmeier et al. (DU145-PSMA) 35 were received from Crescendo Biologics.

Techniques: Inhibition, Expressing, In Vitro, Binding Assay

Journal: Cancer research

Article Title: Increased Tumor Penetration of Single-Domain Antibody Drug Conjugates Improves In Vivo Efficacy in Prostate Cancer Models

doi: 10.1158/0008-5472.CAN-19-2295

Figure Lengend Snippet: 24 hrs after tail vein administration of Alexa Fluor 680 antibody constructs dosed at the same level as the efficacy studies, DU145-PSMA xenografts were frozen in OCT and processed for histology. Blood vessels, shown in red, were ex vivo labeled with Alexa Fluor 555 anti-CD31 antibody while penetration of Alexa Fluor 680 antibody constructs is shown in green.

Article Snippet: Cell Culture and Animals The DU145 cell line (RRID: CVCL_0105, PSMA negative, certified by ATCC via STR analysis) and PSMA transfected DU145 cell line generated by Kampmeier et al. (DU145-PSMA) 35 were received from Crescendo Biologics.

Techniques: Construct, Ex Vivo, Labeling

Journal: Clinical Cancer Research

Article Title: CB307: A Dual Targeting Costimulatory Humabody V H Therapeutic for Treating PSMA-Positive Tumors

doi: 10.1158/1078-0432.CCR-23-3052

Figure Lengend Snippet: CB307 design and induced T-cell phenotypes. A, Illustration of CB307 format: three V H domains separated by peptide linkers. B, PSMA expression on cell lines. DU145-PSMA is isogenic to DU145-Parent other than for constitutive stable PSMA expression. C, Schematic of a Jurkat-based CD137 agonism reporter system whereby CB307 confers the clustering status of PSMA upon CD137 to generate a CD137 agonist signal. CD137 signaling is measured by luciferase expression from an NFκB-based reporter gene. D, Comparison of the reporter gene signal in the presence (DU145-PSMA) and absence (DU145-parent) of PSMA expression. E, Schematic of a primary cell CD137 activity assay whereby PBMCs stimulated by plate-bound αCD3 are co-incubated with tumor cells in the presence of CB307, leading to ( F ) PSMA-dependent secretion of IFNγ, ( G ) PSMA-dependent production of granzyme B, and ( H ) PSMA-dependent production of Bcl.xL. I, PSMA-dependent proliferation indicated by Ki67 expression. J, CB307 pharmacodynamic effects on NK cells. Statistical significance of CB307 treated versus untreated outcomes with PSMA-expressing tumor cells is indicated: **, P < 0.01; ****, P < 0.0001.

Article Snippet: An isogenic PD-L1 gene knockout version of the DU145-PSMA cell line was commissioned using CRISPR technology (Synthego).

Techniques: Expressing, Luciferase, Comparison, Activity Assay, Incubation