Patient Heal Thyself: Researchers are Turning Skin Cells into Cancer Killers

June 21, 2016

Turning Skin Cells into Cancer Killers

A Devastating Diagnosis

For patients diagnosed with glioblastoma, the prognosis is rarely good.  An especially aggressive form of brain cancer, its finger-like tentacles spread rapidly throughout the brain making its surgical removal nearly impossible. Treating the cancer with existing drug therapies is equally frustrating.  The brain's natural barrier against blood-borne pathogens also blocks most therapeutic treatments. That currently leaves an estimated 14,000 people who are diagnosed with glioblastoma each year in desperate need of something better. Within 18 months, 70% of them will die. After five years, fewer than 10% will remain alive, and those who do will suffer from a range of symptoms, from severe headaches and nausea to vision, speech, and cognitive issues. 1 These patients have little left to hope for short of curing themselves.

The "Miracle" Workers

As far-fetched as that idea may seem, learning more about the work of Dr. Shawn Hingtgen's laboratory at the UNC-Chapel Hill Eshelman School of Pharmacy, may well restore your faith in medical miracles.

"Glioblastoma patients desperately need something better, and we are trying to provide that with a better drug-delivery system," Hingtgen says. 2 The drug-delivery system Hingtgen mentions is actually better than "better." Derived from the patients' own skin cells, or fibroblasts, the resulting system is considered the ideal personalized cell therapy.

The whole idea was inspired by Nobel prize-winning research in cell reprogramming. Hingtgen and his associates used the transdifferentiation (TD) process detailed in that research to genetically convert patients' own skin cells into something called induced neural stem cells, known as iNSCs. Hingtgen's team then took those findings a giant step further to achieve a major medical breakthrough of their own. They engineered the iNSCs cells (derived from lab mice) to carry optical reporters and tumor-killing proteins that would innately seek out and kill cancer wherever it is found in the brain. The accomplishment is being called everything from "a significantly more effective treatment for glioblastoma," 3 to the first major advance in the battle against the disease in more than 30 years. 4

How It All Works

Creating a new cancer therapy takes more than just reengineering stem cells and surgically implanting them into a patient's brain. They need a structure to help prolong their lives long enough to do their intended job. In this case, Hingtgen and his staff added the cells to an FDA-approved fibrin sealant that is often used as surgical glue. Small patches of the fiberous protein sealant were then inserted into the cavity left behind following the tumor's removal. That procedure not only tripled the life span of the stem cells, it significantly increased the survival rate of the test mice. 5 The technology proved so successful, in fact, that it is already in development for a possible new type of surgical bandage that will be treated with the cancer-killing cells.

"Our goal is to get this therapy to physicians and patients as quickly as possible, so we wanted to see if we could successfully incorporate it into a product that is already FDA approved for use in people," Hingtgen said. 6

The Importance Of In Vivo Imaging

How can Hingtgen's lab be so confident that its iNSC technique is both effective and repeatable?

"Central to our research is the extensive use of non-invasive imaging," Hingtgen said. Drawing on real-time images and video of preclinical lab mice undergoing treatment, Hingtgen's Targeted Cellular Therapeutic & Imaging Lab tracked the iNSCs' efficacy using the PerkinElmer® IVIS® Kinetic Optical Imaging System along with PerkinElmer's Living Image® 4 Software. Working together, the system provided researchers with "real-time dynamic feedback on stem cell and tumor cell volumes and distribution, pharmacokinetics of drug delivery, and the overall effectiveness of … therapeutic approaches." 7

"We wanted to find out if these directly reprogrammed induced neural stem cells would home in on cancer cells and whether they could be used to deliver a therapeutic agent," Hingtgen said in a recent interview. "They do, and they can. This is the first time the iNSC technology has been used to treat cancer." 8

Equally important, the research of Hingtgen's Targeted Cellular Therapeutic & Imaging Lab has already led to initial iNSC-based clinical trials for primary and recurring glioblastoma. It will soon also be used in clinical trials for breast cancer and neuroblastomas – two additional, autologous examples that patients can indeed heal themselves.

Disclaimer: PerkinElmer's IVIS® Kinetic Optical Imaging System and Living Image® 4 Software are for research use only. Not for use in diagnostic procedures.

References

  1. American Brain Tumor Association, Brain Tumor Statistics.
  2. David Etchison, "UNC Scientists First to Hunt Brain Cancer with Skin Cells Converted to Stem Cells," UNC Eshelman School of Pharmacy, February 24, 2016.
  3. Genetic Engineering & Biotechnology News staff, "Turning Skin Cells Into Cancer Hunters," GEN, February 25, 2016.
  4. UNC, "UNC-Chapel Hell Researchers Make Groundbreaking Discovery, Use Skin Cells To Kill Cancer," UNC News Release, February 24, 2016.
  5. Juli R. Bagó, et al. "Therapeutically Engineered Induced Neural Stem Cells Are Tumour-Homing And Inhibit Progression Of Glioblastoma," Nature Communications,7, No. 10593, February 2, 2016.
  6. UNC, "UNC-Chapel Hill Researchers Make Groundbreaking Discovery, Use Skin Cells To Kill Cancer," op.cit.
  7. Eshelman School of Pharmacy, Targeted Cellular Therapeutic & Imaging Lab, University of North Carolina.
  8. Ibid.

Read More Stories Like This One

Tracking Elusive Breast Cancer Cells

New research by PerkinElmer confirms that PD-L1 protein expression levels in human breast cancer cells can be quickly and accurately assessed directly with the A...

Innovators in Cancer Immunology: Lymphoma

Cancer researchers are uncovering new insights using our Phenoptics™ Quantitative Pathology Research Solutions. In a lymphoma cancer case study, Dr. Rodig uses t...

Related Products