With a Growing Team of Physician-Scientists, UVA Is Increasing Immunotherapy Trials for Cancer

Lawrence G. Lum, MD, DSc. Courtesy: Coe Sweet Photography

At a Glance

  • UVA Cancer Center welcomes immunotherapy expert Lawrence G. Lum, MD, DSc.
  • Lum is developing a treatment platform that can be adapted to a wide range of cancers.
  • Within the next six to 12 months, Lum will launch clinical trials using this platform for pancreatic cancer, metastatic breast cancer and neuroblastoma.

The fight against cancer continues along a number of fronts. The last decade has seen steady advances in the effectiveness of the three cornerstone cancer treatments — surgery, chemotherapy and radiation — and the introduction of targeted therapies like Gleevec® and Herceptin®.

This year, UVA Health System is committed to opening yet another front in this battle, recruiting Lawrence G. Lum, MD, DSc, an expert in immunotherapy, to join its longstanding team of researchers, which includes Craig Slingluff, MD, and Victor Engelhard, PhD. As the scientific director of bone marrow transplantation at UVA Cancer Center, one of Lum’s priorities is pioneering a new method of activating the body’s own T cells to target tumor cells.

“Immunotherapy has tremendous potential,” Lum says. “With support from the health system, I will be able to extend my preclinical research and ongoing clinical trials and launch several new clinical trials of adoptive T cell therapy here at UVA.”

An Adaptable Platform to Deliver Immunotherapy
Rather than create a therapy for a specific form of cancer, Lum is developing a platform that can be adapted to a wide range of cancers. One challenge for immunotherapy is that cancer cells can evolve a number of defenses against it. They can put “blinders” on the immune system, making it difficult for T cells to identify and kill them. Or they can secrete proteins that short-circuit the T cell response or suppress T cell activity altogether.

Lum’s method cuts through these defenses. He constructs a bispecific antibody, a protein built of fragments of two different monoclonal antibodies. One antibody binds to the T cell’s CD3 receptor, which is responsible for activating the immune response. Lum can formulate the other antibody to bind to antigens that are characteristically expressed or overexpressed by cancer cells. This could be HER2 for ovarian, prostate, brain and pancreatic cancer; EGFR for pancreatic, colorectal or brain cancer; or GD2 for neuroblastoma, a form of pediatric cancer.

Instead of formulating a unique monoclonal antibody for the tumor-targeting end of the bispecific antibody, Lum uses existing antibodies that have been approved or are undergoing clinical trials. For instance, he turns to Herceptin for HER2. “I want to create a generic platform that could be adapted to treat different forms of cancer quickly and inexpensively,” Lum says.

To deliver the therapy, Lum extracts T cells from a patient, cultures them to increase their population, coats them with a bispecific antibody engineered to bridge to a specific target antigen on their cancer cells, and then infuses them into the patient. When the T cell contacts the tumor, the T cell secretes factors that enhance the ability of the body’s immune cells to react to tumor antigens released by the killing process, leading to immunization of the patient against their own tumor. “Our goal is to make the T cell a better killer and create lasting immunity while minimizing any side effects,” Lum says. Within the next six to 12 months, Lum will have launched clinical trials using this platform for pancreatic cancer, metastatic breast cancer and neuroblastoma. Preparations for a trial for multiple myeloma also are under way.

The Next Generation of UVA Physician Scientists
With his combination of clinical and research skills, Lum exemplifies the kind of physician scientist UVA is actively recruiting across disciplines. David Wilkes, MD, dean of UVA’s School of Medicine has committed to making 32 such strategic hires in the next four years in such areas as cancer, neurosciences and cardiovascular disease, as well as in such disciplines of organ transplant, regenerative medicine, metabolic disorders and precision medicine.

“By growing our team of exceptional physician-scientists, we stand poised to bridge the gap between world-class science and breakthrough innovation for patients,” Wilkes says.