New CAR-T cell therapy shows promise for treating osteosarcoma

Finding an effective treatment for osteosarcoma, the most common type of bone cancer in children and young adults, has puzzled medical researchers for 40 years.

Now, a new study by researchers at Case Western Reserve University and University Hospitals show some promising results.

The study, published in BMC Medicine, found that a specially engineered immune-cell treatment, called OSM CAR-T, successfully attacks osteosarcoma tumors in mouse models.

Osteosarcoma mainly strikes children, teenagers and young adults during periods of rapid bone growth, with about 1,000 new cases diagnosed nationally each year, according to The Osteosarcoma Institute.

The cause is unknown, but apparently linked to DNA changes in bone-forming cells and, in rare cases, genetics, according to the American Cancer Society.

For the past 40 years, conventional therapies for osteosarcoma, which consist of chemotherapy and surgery, have not changed much. Our new approach offers the possibility of a targeted treatment that harnesses the body's own immune system to fight the cancer-potentially offering better outcomes with fewer side effects than traditional chemotherapy."

Reshmi Parameswaran, study's lead researcher, associate professor in the Department of Medicine at the Case Western Reserve School of Medicine, member of the Immune Oncology Program at the Case Comprehensive Cancer Center, and scientist in the Division of Hematology and Oncology at UH Seidman Cancer Center

CAR-T (Chimeric Antigen Receptor T-cell) therapy is an advanced treatment that reprograms a patient's immune cells to recognize and destroy cancer cells. While CAR-T has revolutionized treatment for blood cancers like leukemia and lymphoma, it has proven far less effective against solid tumors like osteosarcoma.

The National Cancer Institute (NCI) notes that cancer cells in solid tumors are more complex, displaying different markers on their surfaces, which makes it difficult for CAR-T cells to find and attack all the cancer cells effectively.

But the research team solved this problem by creating a CAR-T cell that targets receptors of a protein-called Oncostatin M (OSM)-that appears on the surface of osteosarcoma cells. It represents a new approach to treat osteosarcoma, allowing the engineered immune cells to identify multiple receptors on cancer cells simultaneously.

"The OSM CAR-T cell therapy showed anti-tumor effects against all osteosarcoma patient samples tested," Parameswaran said. "Tumor cells spreading to other organs in the body is a serious problem in osteosarcoma patients, making them non-responsive to most existing therapies. OSM CAR-T cells were effective in killing tumor cells spread to other organs in mouse models, which brings hope to these patients."

Case Western Reserve's collaborative research environment and institutional support made this discovery possible. The university's Comprehensive Cancer Center and University Hospitals provide the infrastructure, expertise and resources necessary to develop innovative cancer immunotherapies.

The team anticipates the treatment will be tested in clinical trials within two years. If successful, the therapy could be offered as a new option, reduce the need for surgery and hope for patients with metastatic disease.