Rafael Davalos

Synopsis:

We use biotransport principles to invent new ways to detect and treat cancer.

Description:

cDEP for Cell Isolation: Cancer stem cells (CSCs) are a finite population of cells with the ability to transplant a new tumor from an existing one and are responsible for the metastatic properties of tumors.

Davalos invented and patented contactless dielectrophoresis (cDEP), a robust microfluidic platform that can isolate and enrich rare cell populations from other cells and particulates, while maintaining sterility of the sample for in vivo studies or culturing. Using this platform, Davalos was the first to show CSCs can be isolated from other tumor cells based on biophysical differences.

To determine if unknown subpopulations of CSCs exist, Davalos is developing the ability to isolate cells based entirely on cDEP without preconceived notions of CSC populations, enabling discovery of new cell type subpopulations and giving researchers the tools needed to help find a cure. Other potential applications include the isolation of stem cells from adipose tissue, isolation of bacteria from blood, and drug screening.

INSPIRE™: Malignancies of the central nervous system are the leading cause of cancer-related deaths in children and adolescents. One of the most prevalent is Malignant Glioma (MG), particularly Glioblastoma Multiforme (GBM). GBM is the most aggressive form and is considered incurable with conventional therapies, resulting in a grim 5-year survival rate less than 5%, typically resulting in death within the first 15 months after diagnosis. One of the main reasons for poor survival is the migration and continued growth of glioma cells several centimeters beyond the margins of the detectable tumor into the peritumoral penumbra of normal appearing brain.

Davalos co-invented and patented Integrated Nanosecond Pulsed Irreversible Electroporation (INSPIRE™), a non-thermal procedure in which MRI-compatible surgical probes are inserted into the target area and emit nanosecond biphasic bursts of electric pulses for tumor ablation. INSPIRE™ provides for more effective treatment of MGs by fulfilling the need for a targeted ablation modality that can treat any location in the brain, including malignancies close to the skull and even encasing critical structures, followed by a transient disruption of the BBB to allow delivery of therapeutics to infiltrative tumor cells.

Through 2-mm burr holes, small surgical electrodes (1-mm) are temporarily inserted into the tumor site to deliver non-thermal pulsed electric fields for about 5 minutes. Results have shown that malignant cells are almost twice as susceptible as healthy cells to the delivered energy, indicating that INSPIRE™ can be used to ablate the bulk of the tumor while selectively killing infiltrative cancer cells, thereby sparing the surrounding healthy brain tissue. Additionally, we are exploring its potential in immunotherapy, and researchers are demonstrating its ability to combat other neurological disorders, such as epilepsy, Alzheimer’s and Parkinson’s Disease.

Modulating Anti-tumor Immunity: Over the last decade, immunotherapy has emerged as a highly promising treatment strategy for many types of cancer. However, the immunosuppressive tumor microenvironment associated with pancreatic cancer presents a significant challenge. Thus, novel treatment approaches that can reverse local immunosuppression; activate the innate immune system; and engage the adaptive immune system to improve cancer cell killing and the eradicatation of micro-metastatic cells/lesions would be expected to dramatically improve patient responsiveness to immunotherapeutics.

We have shown in mice that treatments are significantly more effective in animals with an intact immune system and immunocompetent animals are more resistant to tumor re-challenge. Likewise, in human pancreatic cancer patients, we have observed increased evidence of systemic immune system activation following IRE treatment. Furthermore, we have recently shown the potential to detect and predict in real time a positive immune response in these patients which could facilitate personalized medicine.

Our overarching hypothesis predicts that local and systemic efficacy of IRE and INSPIRE™ ablation is associated with immune system activation. The cell death mechanisms following treatment stimulates the local innate immune system, which shifts the tumor microenvironment from an anti-inflammatory to a pro-inflammatory state. The increased innate immune system activation improves antigen presentation at the primary tumor, resulting in the engagement of the adaptive immune system and improved systemic anti-tumor immune responses.