Journal: Cancer Research

Article Title: STING Agonist VB-85247 Induces Durable Antitumor Immune Responses by Intravesical Administration in a Non–Muscle-Invasive Bladder Cancer

doi: 10.1158/0008-5472.CAN-24-1022

Figure Lengend Snippet: VB-85247 induces expression of immune cell–stimulating cytokines and chemokines in vivo . Mice bearing bladder tumors received a single-dose intravesical injection of vehicle or 40 μg (2 mg/mL) VB-85247. Bladder and serum samples were collected at 4 hours, 6 hours, and 6 days. A, Relative fold change in gene expression in bladders of tumor-bearing mice by RT-PCR. Data were normalized to corresponding GAPDH, and fold changes in gene induction were calculated by the comparative C t method. B, Multiplex analysis of cytokines and chemokines in serum. Statistics by the unpaired Student test (two-tailed) for each indicated time point; significances are noted as *, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001; ns, not significant.

Article Snippet: The MB49, a mouse bladder cell line, was purchased from Millipore (SCC148, RRID: CVCL_7076) and transfected in-house with a luciferase-expressing plasmid (MB49-luc) to monitor the growth of orthotopically implanted cells.

Techniques: Expressing, In Vivo, Injection, Gene Expression, Reverse Transcription Polymerase Chain Reaction, Multiplex Assay, Two Tailed Test

Journal: Cancer Research

Article Title: STING Agonist VB-85247 Induces Durable Antitumor Immune Responses by Intravesical Administration in a Non–Muscle-Invasive Bladder Cancer

doi: 10.1158/0008-5472.CAN-24-1022

Figure Lengend Snippet: VB-85247 provides robust efficacy in a mouse model of NMIBC with lasting protection. Mice with established bladder tumors received vehicle or VB-85247 via intravesical instillation once per week for total of five doses (Q7Dx5): days 4, 11, 18, 25, and 32. A, The scatter blot shows the tumor growth over time, before the first dose on day 4, after the first dose on day 7, and after the last fifth dose on day 35. Individual mice are shown. Black bars, medians. B, Bioluminescent images of representative mice from each treatment group on days 4, 7, and 35. C, Kaplan–Maier survival curves for the vehicle control and VB-85247–treated groups. Survival is noted in parenthesis. Statistical significance was determined. D, Tumor kinetics of subcutaneously reimplanted MB49 cells on tumor-free mice initially treated with VB-8524. The number of tumor-free mice that were rechallenged is noted in the parentheses. Age-matched naïve mice were used as control. Mice with tumors 2,000 mm 3 were euthanized. E, Bladder weight with the tumor in individual mice as outlined in C , or treated groups at study termination on day 89. Statistical significance was determined relevant to the vehicle group with one-way ANOVA, followed by the Tukey test. ****, P < 0.0001. F, Representative images of hematoxylin and eosin–stained bladder sections from the naïve control group and the 40 μg VB-85247 group with pathologic evaluation.

Article Snippet: The MB49, a mouse bladder cell line, was purchased from Millipore (SCC148, RRID: CVCL_7076) and transfected in-house with a luciferase-expressing plasmid (MB49-luc) to monitor the growth of orthotopically implanted cells.

Techniques: Control, Staining

Journal: Cancer Research

Article Title: STING Agonist VB-85247 Induces Durable Antitumor Immune Responses by Intravesical Administration in a Non–Muscle-Invasive Bladder Cancer

doi: 10.1158/0008-5472.CAN-24-1022

Figure Lengend Snippet: VB-85247 is markedly superior to BCG treatment in the mouse model of NMIBC. Mice bearing bladder tumors were treated with 1 mg BCG or 50 μg VB-85247 via intravesical delivery once per week for total of five doses (Q7Dx5): days 4, 11, 18, 25, and 32. A, Tumor growth kinetics of MB49-luc cells based on BLI signal on days 4, 7, and 35. Individual mice are shown. Black bars, medians. Statistical significance was determined relevant to the control vehicle group with one-way ANOVA, followed by the Tukey test on day 7, **, P < 0.0039. B, Kaplan–Maier survival curves for the vehicle control and VB-85247 treatment groups. The surviving animals at the end of the study are noted from the number of animals at the start of the experiment.

Article Snippet: The MB49, a mouse bladder cell line, was purchased from Millipore (SCC148, RRID: CVCL_7076) and transfected in-house with a luciferase-expressing plasmid (MB49-luc) to monitor the growth of orthotopically implanted cells.

Techniques: Control