Pre-clinical Data
On December 9, 2024, a groundbreaking study led by Dr. Rajan Gogna’s team at Virginia Commonwealth University (VCU) was published in Nature Biotechnology. (accessible here) The study unveils a novel mechanism by which ovarian tumor cells gain a competitive edge in the tumor microenvironment (TME), shedding new light on cancer progression and offering hope for early detection.
The number of GFP+ spots was measured in 3D printed scaffolds populated with OVCAR8 cells and human stromal cells. Scaffolds treated with Flower mAb had significantly lower GFP+ signal, highlighting attenuation of tumor growth with therapy (p < 1x10-10).
Schematic outline of antibody experiment in an orthotopic murine model. Human derived HGSC cells were tagged with luciferase and orthotopically injected into ovaries of NSG mice. One cohort of mice received an intravenous injection of the Flower mAb (40 mg/kg) at 10, 12, 15, 20, 25, 35, 45, and 55 days. The other mice were either untreated, vehicle treated, or IgG antibody treated. At 60 days, all remaining mice were imaged and euthanized for organ harvest.
Two patient derived xenografts (PDX1 and 2) with luciferase tags were orthotopically implanted into NSG mice, subjected to various treatments, and tracked via IVIS. Columns 1-3 show IVIS images from control, vehicle treated, and IgG treated mice respectively. Columns 4 and 5 highlight impact of treatment with Flower mAb alone and standard of care chemotherapy (Docetaxel/Carboplatin) respectively. Column 6 shows results of treatment with Docetaxel/Carboplatin with IgG. Columns 7 and 8 demonstrates synergy of Docetaxel/Carboplatin with Flower mAb and Bevacizumab respectively. Column 9 shows the demonstrates the impact of combining all therapies (Docetaxel/Carboplatin/Flower mAb/Bevacizumab). Overall, Flower mAb can attenuate tumor growth as a monotherapy and in combination with standard chemotherapy.
NSG received orthotopic injections of OVCAR4 and OVCAR cells. Representative tumors from each cohort are shown. Tumors treated with standard chemotherapy had smaller tumors compared to control and vehicle-treated tumors. The addition of Flower mAb further diminished tumor size.
Tumor volumes of the PDX1 and PDX2 cohorts tracked over time with 95% confidence intervals demonstrate the ability of Flower mAb to decrease tumor growth as a single agent and in combination with standard chemotherapy. The first column shows the growth curves for control, vehicle, and IgG treated mice. The second column demonstrates the impact of standard chemotherapy regimens on tumor growth. The third column shows further Madan et. al. 53 attenuation of growth rate with addition of Flower mAb. The p-values shown compare tumor volumes at the endpoint of the experiment of mice untreated mice with Docetaxel/Carboplatin and Bevacizumab treated (PDX1: p = 6.7x10-4 ; PDX2: p = 1.0x10-5), and Flower mAb (PDX1: p = 5.x10-4 ; PDX2: p = 9.9x10-7 ). The number of mice use in each group was equal to 5.
Heatmap demonstrating impact of Flower mAb on tumor metastasis. The number of on each column corresponds to the group noted in the labelling key. As shown, standard chemotherapy reduces the number of metastatic lesions. Addition of Flower mAb further decreases the number of lesions. L) Kaplan-Meier analysis of each of the PDX1 and PDX2 cohorts demonstrates the impact of Flower mAb treatment on survival. The color of each line represents a treatment cohort corresponding to the labelling key. Mice that received treatment with Docetaxel/Carboplatin/Bevacizumab/Flower mAb had the highest survival rate, with 80% survival at the end of the experiment. (PDX1: p = 1.7x10-3 ; PDX2: p = 1.8x10-3 ).