Funding will advance novel approaches to treating cancer and diabetes-related blindness
The Dr. Ralph and Marian Falk Medical Research Trust awarded a combined $1.35 million to two researchers from Case Western Reserve University School of Medicine to advance their work on finding more effective treatments—and better options—for two debilitating diseases.
The Falk Trust awarded Reshmi Parameswaran, an assistant professor in the Department of Medicine, Division of Hematology/Oncology, pathology and pediatrics at the School of Medicine, $1 million over three years for her work in cancer cell therapy.
Carlos Subauste, a professor of medicine and pathology at the School of Medicine, received a two-year, $350,000 grant for his research in diabetic retinopathy, a leading cause of blindness.
Cancer cell therapy
Parameswaran has developed a new treatment strategy for B-cell cancer patients—especially for those who don’t respond to conventional therapies. B-cell lymphoma is a type of cancer that forms in white blood cells.
Many B-cell cancer patients don’t respond to existing therapies, and the disease returns in about half of these patients. Some patients don’t respond at all, while others may initially respond well, but then the disease returns those therapies are ineffective. About 100,000 of the 250,000 B-cell cancer patients diagnosed annually in the United States need a more effective therapy option.
Parameswaran—also a member of the Immune Oncology Program at the Case Comprehensive Cancer Center—is building modified immune cells that have more power to kill cancer cells, without killing normal cells, and minimizing side effects. This cell therapy then could be easily injected into patients.
To build these cells, Parameswaran purifies “Natural Killer (NK)” cells—white blood cells with tumor-killing capabilities. Then a piece of DNA, called “BAFF CAR,” is inserted, which she said gives the NK cells more “specificity” and “power” to kill cancer cells, sparing normal cells.
NK cells from any donor can be used to make BAFF CAR-NK cells, she said, and when a need arises, these specialized cells can be thawed and injected into patients. Her lab hopes to validate the tumor-killing potential and safety of BAFF-CAR NK cells using mouse models with the support from the Falk Trust.
“Both pharmaceutical companies and clinicians treating B cell cancer patients have expressed a strong interest in the BAFF CAR-NK cells as a needed therapeutic,” Parameswaran said. “With this funding, we are optimistic to get this product to the clinic within three years.”
Diabetic retinopathy
Nearly 700 million people will be diagnosed with diabetes worldwide by 2040, and more than a third will develop diabetic retinopathy, Subauste said.
Diabetic macular edema, caused when blood vessels in the retina leak, is a major reason for progressive loss of vision in diabetic patients.
The disease is treated with eye injections of agents that neutralize what is called Vascular Endothelial Growth Factor (VEGF). But the treatment is only effective in about half of the patients, he said, because other inflammatory molecules can also cause the blood vessels to leak. Anti-VEGF agents only target VEGF, likely explaining why they are partially effective in treating diabetic macular edema.
Subauste and his colleagues are developing a drug that inhibits the molecule CD40, which is known to increase the production of both VEGF and inflammatory molecules in the diabetic retina.
Preliminary studies in the retinas of diabetic mice models suggests this approach may be more effective than monthly injections of anti-VEGF agents.
“Our work is positioned to lead to a novel and more effective way to treat diabetic retinopathy and avoid vision loss, without requiring monthly intra-ocular injections,” he said.
The Dr. Ralph and Marian Falk Medical Research Trust supports biomedical research with two programs: the Catalyst Research Award Program that provides seed funding to develop promising concepts, and the two-year Transformational Research Award to help researchers advance these concepts toward commercial development.
These new awards build on the previous seven Falk Trust awards to Case Western Reserve biomedical researchers, totaling $3.5 million.
For more information, contact Bill Lubinger at william.lubinger@case.edu.
This article was originally published Nov. 16, 2023.