Abstract 524: The novel STING agonist VB-85247 induces robust durable antitumor immune responses by intravesical administration in a non-muscle invasive bladder cancer model

2021 ◽  
Author(s):  
Miglena Prabagar ◽  
Venu Bommireddy ◽  
Rachael Siegel ◽  
Haihua Zheng ◽  
Lee Pellegrino ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Immune Responses ◽  
Invasive Bladder Cancer ◽  
The Novel ◽  
Cancer Model ◽  
Intravesical Administration ◽  
Muscle Invasive Bladder Cancer ◽  
Muscle Invasive ◽  
Bladder Cancer Model

Tumor burden reduction in an orthotopic non-muscle-invasive bladder cancer model using IL-15 analogue (ALT-803) targeting T regulatory cells.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 298-298
Author(s):  
Evan Gomes ◽  
Makito Miyake ◽  
Ge Zhang ◽  
Steve Goodison ◽  
Jack Egan ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Nk Cells ◽  
Tumor Burden ◽  
Invasive Bladder Cancer ◽  
Intravesical Therapy ◽  
Cancer Model ◽  
Muscle Invasive Bladder Cancer ◽  
Bcg Therapy ◽  
Muscle Invasive ◽  
Bladder Cancer Model

298 Background: A recent NCI review listed IL-15 as the most promising product candidate among twelve immunotherapy drugs that could potentially cure cancer. Preclinical studies using ALT-803 (mutated IL-15 analogue combined with IL-15Rα-Fc fusion) have shown promising results for obtaining prolonged drug half-life and stimulating CD8+ T cells and NK cells. Based on these results, we hypothesized that the administration of ALT-803 will generate an immunologic response which will reduce tumor burden in a rodent carcinogen induced orthotopic non muscle invasive bladder cancer model (NMIBC). Methods: We tested intravesical ALT-803 alone and ALT-803 in combination with Bacillus Calmette-Guérin (BCG) in a rodent carcinogen induced orthotopic NMIBC model. Rats were anesthetized then a 22-gauge Teflon transurethral catheter was placed in the bladder and urine completely drained from the bladder. Next, the saline (negative control), ALT-803 (experimental agent) or BCG (positive control) therapy was delivered by transurethral instillation and allowed to dwell in the bladder for 1 hr by occlusion of the urethra with a purse string suture. The intravesical therapy was administered weekly for a total of six weeks to mimic intravesical BCG therapy in humans. Results: Herein we demonstrate that ALT-803 was safe and well tolerated alone or in combination with BCG. Furthermore, ALT-803 alone reduced tumor burden by 23% whereas BCG alone reduced tumor burden by 11% compared to control. The combination of ALT-803 and BCG reduced tumor burden by 30% compared to control. Tumoral responses of the combinational treatment were associated with 76% and 80% reduction in angiogenesis and proliferation, respectively, whereas combinational therapy was associated with a 7.7-fold increase in apoptotic index compared to control. Immune monitoring suggested that the antitumor response was linked to the activation of CD8+ cells and NK cells. Conclusions: The enhanced therapeutic index provided by ALT-803 plus BCG therefore provides a powerful justification for the development of this agent for future clinical trials in subjects with non-muscle invasive bladder cancer.

scholarly journals BioXmark® liquid fiducial markers for image-guided radiotherapy in muscle invasive bladder cancer: a safety and performance trial

2020 ◽  
Vol 93 (1111) ◽  
pp. 20200241
Author(s):  
Mischa de Ridder ◽  
Lara C Gerbrandy ◽  
Theo M de Reijke ◽  
Karel A Hinnen ◽  
Maarten C.C.M. Hulshof
Keyword(s):  
Bladder Cancer ◽  
Learning Curve ◽  
Fiducial Marker ◽  
Invasive Bladder Cancer ◽  
The Novel ◽  
Muscle Invasive Bladder Cancer ◽  
Image Guided Radiotherapy ◽  
Promising Tool ◽  
And Performance ◽  
Muscle Invasive

Objective: This study evaluated the performance of the novel liquid fiducial marker (BioXmark®) in IGRT for bladder cancer. Methods: 20 patients with muscle invasive bladder cancer were entered in this prospective, single center, Phase I-II study. The novel BioXmark® liquid markers were injected around the tumor using a flexible cystoscopy. Visibility and stability of the markers were evaluated on planning-CT and CBCT. Prospectively defined threshold for success was set at a visibility of 75%. Results: In total, 76 markers were implanted in 20 patients. Of those, 60 (79% 95% CI ± 9%) were visible on CT scan. Due to the learning curve of the technique, the visibility improved in the last 75% of patients (86% visibility) compared to the first 25% of patients with 58% visibility. Concerning stability of the BioXmark® marker, all visible markers after CT acquisition were still detectable at the last CBCT without displacement. In 15/20 (75%) of the patients, three or more markers were visible on CT. No BioXmark® related adverse events were reported. Conclusion: The success rate of this novel fiducial marker was 79%, which is above the prospectively defined threshold rate. A distinct learning curve of the injection of the liquid marker was seen over the study period. The marker showed sustained visibility and positional stability during treatment phases and also appears to be safe and easy to inject. Advances in knowledge: This novel liquid BioXmark® marker seems to be a very promising tool in daily-adaptive IGRT for bladder preserving chemoradiotherapy in muscle invasive bladder cancer.

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