This SBIR project brings together the skills and resources of laboratories at Scion Cardio-Vascular Inc. (Scion C-V), Loma Linda University, and North Carolina State University to advance a new signaling molecule treatment for superficial bladder cancer. This treatment delivers the cytokine Interleukin 12 (IL-12) to the bladder wall using Scion C-V's mucoadherent, depyrogenated chitosan (Ch) hydrogel (Ch+IL-12) as the vehicle. Therapeutic effectiveness of the depyrogenated Ch+IL-12 hydrogel will be studied in a relevant mouse bladder cancer model, replicating the pre-clinical studies performed at the National Cancer Institute (NCI). The NCI studies showed remarkable cures of bladder cancer in a mouse model treated with intravesicular Ch+IL- 12. The NCI was preparing to test treatment of superficial bladder cancer with Ch+IL-12 in a controlled clinical trial but cancelled the study because of widespread pyrogen contamination in commercially available "medical grade" chitosans. Pyrogen contamination is a well recognized problem that limits the applicability of chitosan as an excipient for implantable biomedical applications. There is an urgent need to define versatile alternative, methods that reduce the systemic toxicity of chitosan and IL-12 to improve bladder cancer immunotherapy. We have found that treating chitosan with non-thermal atmospheric nitrogen gas plasma (NtANP) both reduces chitosan endotoxins and may enhance mucoadhesion. As a Phase I study, we will test the hypothesis that our NtANP technology will enable an FDA approved safe and economical Ch+IL-12 delivery vehicle.

Public Health Relevance

There is an urgent need to improve bladder cancer immunotherapy by alternative delivery methods that reduce the systemic toxicity of chitosan and Interleukin-12 (IL-12). We have found that treating chitosan with non-thermal atmospheric nitrogen gas plasma (NtANP) reduces chitosan endotoxins and may enhance mucoadhesion of the drug combination with IL-12. As a Phase I study, we will test the hypothesis that our NtANP technology will enable an FDA approved safe and economical Ch+IL-12 delivery vehicle to treat mouse bladder cancer.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Small Business Innovation Research Grants (SBIR) - Phase I (R43)
Project #
1R43CA186374-01A1
Application #
8781774
Study Section
Special Emphasis Panel (ZRG1-OTC-H (13))
Program Officer
Weber, Patricia A
Project Start
2014-08-11
Project End
2015-07-31
Budget Start
2014-08-11
Budget End
2015-07-31
Support Year
1
Fiscal Year
2014
Total Cost
$225,000
Indirect Cost
Name
Scion Cardio-Vascular, Inc.
Department
Type
DUNS #
007530459
City
Miami
State
FL
Country
United States
Zip Code
33186