Dec. 12, 2023
Researchers at Mayo Clinic have developed a new type of chimeric antigen receptor (CAR)-T cell therapy (CAR-T cell therapy) focusing on eradicating B cell blood cancers that have recurred or are unresponsive to existing treatments. Hong Qin, M.D., Ph.D., a researcher at Mayo Clinic in Jacksonville, Florida, and his team designed and developed a pioneering technology that has shown effectiveness in eliminating B cell tumors grown in the laboratory and tumors implanted in mouse models.
Preclinical results were published online in Cancer Immunology, Immunotherapy in October 2023.
"Our goal is to develop new therapies for those patients who have exhausted currently available treatment options."
CAR-T cell therapy has shown potential in achieving remission in some B-cell lymphomas and leukemias. Yet, challenges persist with cancer relapsing in approximately 40% of patients within two years post-therapy.
Currently, six different CAR-T cell therapies are approved for treating relapsed blood cancers. Most patients have impressive response rates, but not everyone responds to treatment. "Our goal is to develop new therapies for those patients who have exhausted currently available treatment options," says Dr. Qin.
New CAR-T cell therapy development
Dr. Qin's team has developed a therapy targeting the B cell activating factor receptor (BAFF-R), prevalent in patients with B cell cancers, especially those with chronic lymphocytic leukemia. The BAFF-R protein is associated with tumor growth, and this innovative therapy is designed to empower the immune system to combat tumors that have returned or are resistant to available CAR-T cell therapies.
Dr. Qin's team developed a method for isolating T cells and tumor cells from three patients with chronic lymphocytic leukemia blood samples. The team generated BAFF-R targeting CAR-T cells from the individual samples and then demonstrated in the lab that these genetically modified cells could kill tumors using patients' own cells.
"This preclinical study shows our experimental CAR-T cell therapy targets several blood cancers, specifically chronic lymphocytic leukemia," says Dr. Qin.
Transition to biomanufacturing: Accelerating promising new therapies
Results of this early research have set the stage for Mayo Clinic to begin biomanufacturing this experimental CAR-T cell therapy in Florida. The next step involves moving these CAR-T cells into a phase 1 clinical trial to evaluate safety and define the treatment dose in humans. It is anticipated that it may take 5 to 7 years to make this therapy clinically available, depending on the outcomes of the phase 1 trial.
Developing and manufacturing BAFF-R targeted CAR-T cell therapy on-site offers unique advantages. In-house biomanufacturing allows for dose customization, personalized treatments and faster delivery to patients.
"The cornerstone of Mayo's biomanufacturing strategy is accelerating promising new medicines from human sources such as cells to patient care. Biomanufacturing CAR-T cells is a high priority because of the potential to provide healing for patients with few or no other solutions," says Julie G. Allickson, Ph.D., the Michael S. and Mary Sue Shannon Family Director for Regenerative Biotherapeutics at Mayo Clinic in Rochester, Minnesota. "We are very excited to reach this landmark of biomanufacturing the first CAR-T cell therapy developed by Mayo Clinic research."
In partnership with Mayo Clinic's Hematology and Medical Oncology and Mayo Clinic Comprehensive Cancer Center in Florida, Mayo Clinic's Center for Regenerative Biotherapeutics is committed to introducing novel cell therapies for complex conditions.
Mayo Clinic is expanding its biomanufacturing facilities on all three campuses, aiming to rapidly transition cell therapies from research labs to early-stage clinical trials. The goal is to collaborate with industry partners to introduce new regenerative immunotherapies into standard clinical practice to benefit patients worldwide.
For more information
Luo Y, et al. Translational development of a novel BAFF-R CAR-T therapy targeting B-cell lymphoid malignancies. Cancer Immunology, Immunotherapy. In press.
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