Despite significant advances in chemotherapeutic approaches due to new drugs and combinatorial therapies over the past decades, cancer is still the second leading cause of death in the United States. Further, pancreatic cancer is one of the most aggressive and deadly cancer types, with only a 7% chance of patient survival five years past diagnosis. In this Phase I SBIR proposal, the Tubular Plasma ReactorTM (TPR) platform developed by Symbios Technologies, Inc. will be used to generate reactive plasma species in aqueous solutions via a low-temperature plasma discharge. This technology encompasses the formation of aqueous plasma chemotherapeutic (APC) solutions, which are intended to be applied for selective pancreatic cancer cell modification to address critical cancer therapy needs. The TPR platform enables the environmentally friendly production of APC to provide clinicians with the flexibility of multiple routes of administration. The formation of plasma species within aqueous solutions sets TPR- generated APC apart from other plasma-based technologies. More specifically, previous work has shown that the use of gas-phase plasma plumes directed on cell cultures resulted in the selective inhibition of pancreatic cancer cell growth, while not harming normal endothelial cells. However, such gas-phase plumes restrict the use to topical applications, which are not useful for the treatment of internal tumors. Preliminary data collected by Symbios Technologies employing TPR-generated APC demonstrates the selective, dose-dependent treatment of cancer cells, while normal cells remained viable across all doses. Thus, this proposal is focused on four major goals: (a) optimize APC generation for maximum therapeutic efficacy, (b) expand the investigation of APC to multiple pancreatic cancer lines that exhibit differences in resistance to the current standard treatment, (c) quantify the relevant stable plasma species that contribute to the therapeutic action to inform mechanistic insights and to evaluate shelf-life and serum scavenging, and (d) identify the mechanism of action associated with APC inhibition of cancer cell growth. Overall, the APC preliminary data collected combined with previous literature regarding the therapeutic properties of plasma species supports the hypothesis that the TPR represents a viable platform for generating chemotherapeutic solutions. Thus, Symbios will be the first to combine aqueous plasma chemistry with chemotherapeutic effects to result in a commercially viable cancer treatment modality. Completion of Phase I objectives will make possible in vivo animal cancer models in Phase II.
Public Health Relevance Statement: Because there is a great unmet need for improved pancreatic cancer treatments, Symbios Technologies, Inc. is developing its promising new method for selectively killing cancer cells that uses an aqueous, low-temperature electric discharge plasma system. Prior art demonstrates that cancer cells are selectively damaged by plasma plumes compared to normal cells, but these gas phase plasmas are not practical for treating tumors inside the body. The aqueous plasma chemotherapeutic solutions that are generated by Symbiosâ technology platform to contain therapeutic plasma species show great promise to overcome a major hurdle in the field by representing a new pancreatic cancer treatment modality that demonstrates selective and dose- dependent cancer cell inhibition, as supported by preliminary data.
Project Terms: Address; AlamarBlue; Animal Cancer Model; Animal Model; Apoptosis; aqueous; Arts; base; Biological Assay; cancer cell; Cancer Cell Growth; Cancer cell line; cancer therapy; cancer type; Cancerous; Caspase; Catheters; Cause of Death; Cell Culture Techniques; Cell Death; Cell Line; Cells; Chemistry; chemotherapy; Chemotherapy-Oncologic Procedure; Clinical; cold temperature; combinatorial; commercialization; Data; Diagnosis; Disease; Dose; Endothelial Cells; Exhibits; flexibility; Flow Cytometry; Gases; gemcitabine; Generations; Goals; Growth; Half-Life; Hydrogen Peroxide; improved; in vivo; Inhibition of Cancer Cell Growth; innovation; insight; Investigation; Killings; Life; Literature; Malignant neoplasm of pancreas; Malignant Neoplasms; Measures; Medicine; Methods; Modality; Modification; Necrosis; Nitrates; Nitrites; Normal Cell; novel; novel therapeutics; Oxidants; Ozone; Pancreas; pancreatic cancer cells; Pathway interactions; Patients; Phase; Plasma; Production; Property; Proteins; Reaction; research study; residence; Resistance; response; Route; Running; Serum; Site; Small Business Innovation Research Grant; standard care; success; Surface; System; Technology; Testing; Therapeutic; Time; Tissues; Topical application; Treatment Efficacy; Tubular formation; tumor; United States; Wor
