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Dr. Doug Myers Receives Grant to Study How Tumor Microenvironment Suppress Tumor Killing Capabilities of CAR T Cells

STORIES

Dr. Doug Myers Receives Grant to Study How Tumor Microenvironment Suppress Tumor Killing Capabilities of CAR T Cells

Headshot of Doug D. Myers, MD
Doug D. Myers, MD
Section Chief, Bone Marrow Transplantation; Section Chief, Bone Marrow Transplant & Cellular Therapy; Professor of Pediatrics, University of Missouri-Kansas City School of Medicine; Clinical Associate Professor of Internal Medicine, University of Kansas School of Medicine
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Doug Myers, MD, Hematology/Oncology/BMT, received a one-year, $50,000 2022 Pilot Award from The University of Kansas Cancer Center with a project period ending on Dec. 31, 2023.

The funding is being used for Dr. Myers’ study “Role of macrophages and tumor structure in modulating chimeric antigen receptor (CAR) T-cell activity in solid tumors.”

Survival rates for children with blood cancers have risen dramatically over the years. However, a dramatic new treatment called “Chimeric Antigen Receptor T-cells”, or CAR-T, has been developed to and shown to cure up to 60 percent of children with certain forms of blood cancer that did not respond to traditional chemotherapy and radiation.

Unfortunately, treatment for patients with very aggressive solid tumors, like osteosarcoma, a bone tumor, has not improved survival significantly, even though doctors have given higher doses of chemotherapy and radiation and performed more aggressive surgery.

“Disappointingly, attempts to use CAR-T for these very aggressive solid tumors have not yielded the same impressive improvements in cure rates as for patients with blood cancer,” said Dr. Myers. “We have hope that we can make CAR-T more effective for these patients, but we will need to know more about how these tumors keep themselves safe from the killing effect of CAR-T.”

Scientists now know that our immune system kills cancer cells in our body frequently. T-cells move around in our body and kill cells that have been infected with viruses, so the virus does not spread to other cells. These same T-cells can kill abnormal cells in our body that can become or already have become cancer. If a T-cell can find and attach to a cancer cell, it can kill that cell.

However, cancer cells can change the way they grow and become invisible to our T-cells. They have several complicated tricks to accomplish this. One trick is to communicate with a certain group of our immune cells called macrophages. Macrophages are very important for telling T-cells whether or not to kill cells that are infected with viruses or cells that have become cancerous. Tumors can send out chemical signals that confuse macrophages.

Rather than activating a T-cell to kill a tumor cell, these confused macrophages can tell a T-cell to leave a tumor cell alone allowing the tumor to grow.

“This study will help us learn how tumors can confuse macrophages and how these confused macrophages may be telling CAR-T cells not to kill solid tumor cells,” said Dr. Myers. “This study will help us understand more about how to engineer CAR-T cells to be more effective at killing solid tumors.”

If successful, the team hopes this study could help them one day create CAR-T cells for patients with solid tumors and give them the same, better chance of cure that patients with certain blood cancers now have, thanks to CAR-T.

Dr. Myers will collaborate on this project with Dr. David Akhavan of KU Medical Center. The project will utilize the Children's Mercy Research Institute's new state-of-the-art 3D bioprinter to build multicellular three-dimensional tumor models of osteosarcoma.

The University of Kansas Cancer Center’s Pilot Awards fund promising novel research being conducted by cancer center members.