By Michael Bradley
Special to Delaware Business Times
When Dr. Eric Kmiec speaks about the gene-editing work being done at Christiana Care Health System, he references partnerships often. The hospital has teamed with an Israeli company to create personalized cancer treatments from the research Kmiec and his team are performing.
In addition, Christiana Care is working with Nemours to develop gene-editing therapies to tackle sickle cell anemia and leukemia, and Kmiec said the support of the hospital system’s Helen F. Graham Cancer Center and Research Institute has been instrumental to his work.
But it’s the link between the therapies that are developed and the chemotherapy charged with fighting patients’ cancers that is garnering attention. The breakthroughs that come from Kmiec’s lab will help the oft-used method of killing cancer cells — and plenty else in an affected body — become more successful and less reckless.
“We are using gene therapy to reduce chemotherapy resistance that develops during chemotherapy and also radiation,” Kmiec said. “By reducing the resistance, we can increase the efficacy of chemotherapy.”
The work being done at Christiana Care is part of a larger effort across a variety of hospitals and research centers nationwide. Pioneers like the University of Pennsylvania and MD Anderson Cancer Center at the University of Texas have had success in producing therapies to address blood cancers, like leukemia, as well as glioblastoma, an aggressive brain tumor. Although everyone involved is working hard to create advancements in the field, there is not animosity. The rivalry is friendly, and “we are rooting for all of these folks,” Kmiec said.
At Christiana Care, Kmiec and his team are focusing on lung cancer, which is the leading cause of cancer death in Delaware. While their work will not be curative, it will help reduce some of the toxicity that comes from more traditional treatments and produce more tailored approaches that focus on individuals’ specific conditions.
But instead of trying to reverse the many gene mutations that can occur as cancer goes about its course, the therapies being developed are trying to disable genes so that they cannot work against the patient. To this point, the research has been done in cells and animals, but Christiana Care is nearing the clinical trial stage, which is the precursor to the development of strategies that can be used in people.
“Fixing the gene or repairing the mutation in a cancerous gene is not a good approach, because there are too many mutations,” Kmiec said. “As the tumor grows, it changes and gains mutations.
“Everyone has the same number of genes in their body, and in various types of cancer, some of the common genes are malfunctioning. We are knocking those genes out and tailoring therapy to disable the gene so that the cancer-fighting therapies can be more effective.”
The progress is due in large part to the development of CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats), which allows researchers and physicians to re-engineer DNA and chromosomes in human cells with a tremendous amount of specificity. CRISPR allows scientists to disable a particular gene to reduce or eliminate the resistance to a specific chemotherapy treatment. That allows for the “rifle shot” approach, which creates individual approaches to fighting cancer, rather than hitting every patient with the same cocktail of medicines.
Although this work is extremely new, and the breakthroughs have the potential to be revolutionary, the equipment necessary to do this work is not all that sophisticated, in terms of what already exists. Kmiec reports that there is “almost no new equipment involved” and that the key to the success is the team of researchers, most of whom are young, who are able to use their computer skills to create the new paradigms for cancer care.
“We are able to build the tools in the laboratory and insert them in cells and animals,” Kmiec said. “Great discoveries are usually pretty simple. The gene editing protocol that people are excited about has been occurring in bacteria since the beginning of time.
“The brilliance of people who converted this is that they figured out how to move it from naturally occurring in bacteria to a useful role for humans.”
As Kmiec and his team move closer to creating these gene therapies, Christiana Care has partnered with Israel-based biotechnology company NovellusDx to improve the efficiency of NovellusDx’s cancer diagnostic screening tools. As with many research lab breakthroughs, a second party is needed to help take the discoveries to market, and that’s what this partnership does.
Christiana Care will provide the science, while NovellusDx will take the hospital system’s advancements and “identify the genetic mechanism responsible for both the onset and progression of many types of cancer and determine the most effective cancer therapy,” according to a release. NovellusDx will take the tools provided by Christiana Care and determine which drugs work best for which patients. It’s a further honing of the treatment process, with the two companies providing more and more specific ideas for how to treat individual cases.
The licensing deal will provide a 10-year revenue stream for Christiana Care and was facilitated by a $900,000 grant last December from the U.S.-Israel Binational Industrial Research and Development Foundation.
“We’re involved with helping them figure out the best way to create treatments for patients,” Kmiec said. “I think both parties are very happy.”