Sept. 03, 2025
Researchers at Mayo Clinic have made a promising breakthrough in the development of a novel therapy for solid tumor treatment. Hong Qin, M.D., Ph.D., a researcher at Mayo Clinic in Jacksonville, Florida, and Alfredo Quinones-Hinojosa, M.D., a neurosurgeon and the James C. and Sarah K. Kennedy Dean of Research at Mayo Clinic in Florida, embody the multidisciplinary approach that allows Mayo Clinic to advance care options for all cancers. Their research has resulted in the development of a new kind of CAR-T cell therapy that has shown early success in shrinking and eliminating solid tumors.
Chimeric antigen receptor (CAR)-T cell therapy has already been established as a revolutionary way to treat certain blood cancers, including B-cell lymphomas and leukemias. But scientists have faced unique challenges developing a CAR-T cell therapy that targets solid tumors. CAR-T cells are genetically engineered to recognize specific antigens on the surface of cancer cells, but because tumor cells are diverse, it has been difficult to identify the right antigen to target. Tumors also are surrounded by an immunosuppressive tumor microenvironment (TME) that protects against the therapy.
Dr. Qin and Dr. Quinones-Hinojosa believe they may have found a way around these challenges by developing a therapy that targets programmed death-ligand 1 (PD-L1). PD-L1 is a protein that is commonly overexpressed on the surface of not only tumor cells but also cells in the tumor microenvironment.
"PD-L1 is a very good target for us, because it allows us to simultaneously hit tumor cells and the immunosuppressed cells in the tumor microenvironment," says Dr. Qin. "When we target PD-L1, we can address the issue that's preventing CAR-T cells from entering the tumor."
The team collaborated with Haidong Dong, M.D., Ph.D., a researcher and immunologist at Mayo Clinic, to develop MC9999, a form of CAR-T cell therapy that targets PD-L1.
Once developed, the solid cancer-directed CAR-T cell therapy was tested in four different solid tumor models: breast cancer, lung cancer, melanoma and glioblastoma multiforme (GBM). In all four cases, MC9999 was able to specifically target PD-L1, leading to significant tumor reduction.
The GBM test was particularly notable because of the way the therapy was developed. Unlike the other three tests, which used a CAR-T cell therapy that was generated from healthy donor T cells, the GBM test used patient-derived CAR-T cells from real patients with GBM.
"This is the essence of precision medicine," says Dr. Quinones-Hinojosa. "We're developing a personalized therapy that uses the patients' own cells to treat the tumor. We're fighting cancer with cancer."
The GBM test also was significant because it showed that the therapy could cross the blood-brain barrier, a notoriously difficult obstacle for brain cancer therapies. Results of the study were published in Molecular Therapy: Oncology in October 2024.
The power of a multidisciplinary approach to develop novel CAR-T cell therapies
Both Dr. Qin and Dr. Quinones-Hinojosa emphasized the importance of cross-departmental collaboration for cancer care innovation.
"It's a huge project, to move our therapeutics from the lab to the patient bedside," says Dr. Qin. "Nobody can make that happen without help from others. I think collaborative work is essential for translational research."
The technical facilities available at Mayo Clinic also paved the way for innovation, including on-site biomanufacturing of the new CAR-T cell therapy and access to human tissue through the Biospecimen Accessioning and Processing (BAP) Core.
What's next for CAR-T cell therapy for solid tumors?
Now that the principal studies are complete, the next step is clinical trial. The team has set an ambitious three-year goal to develop the necessary pathways for a safe clinical trial of MC9999 CAR-T cell therapy in humans.
"Our goal is to test this therapy in clinical trial, and we're closer today than we were five years ago," says Dr. Quinones-Hinojosa. "We want to make it happen tomorrow, but we're getting close."
Both researchers are eager to get this treatment into the hands of patients.
"We're doing our work for one reason only: to save patients' lives," says Dr. Qin. "We hope that, through our work, we can eventually extend patients' lifespans, improve their quality of life and eradicate their diseases."
For more information
Luo Y, et al. Solid cancer-directed CAR T cell therapy that attacks both tumor and immunosuppressive cells via targeting PD-L1. Molecular Therapy: Oncology. 2024;32:200891.
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