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$4M Grant Will Help To Advance New CAR T-Cell Therapy

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On November 23, 2021, the California Institute for Regenerative Medicine (CIRM) governing board approved a $4.1 million grant to enable University of California San Diego School of Medicine researchers to advance a new chimeric antigen receptor (CAR) T-cell therapy from the laboratory into the clinic.

In this type of cancer therapy, a patient’s own T-cells, a type of immune cell, are collected from a blood draw and genetically modified in the lab so that they can recognize proteins on tumor cells. After infusion back into the patient, the CAR T-cells kill the targeted cancer cells.

The work will be led by principal investigator Ezra Cohen, MD, professor at UC San Diego School of Medicine, associate director for clinical science and chief of the Division of Hematology-Oncology at Moores Cancer Center at UC San Diego Health, and Charles Prussak, PharmD, PhD, director of the Cell Therapy Translational Laboratory at Moores Cancer Center.

In their previous laboratory studies, Cohen and team developed CAR T-cells that specifically target ROR1, a molecule found on the surface of many cancer cells. ROR1 is normally used only by embryonic cells during early development, but it can also be exploited by cancer cells to promote tumor growth.

ROR1 is also the target of cirmtuzumab, an experimental monoclonal antibody-based drug developed by another UC San Diego School of Medicine research team with funding from CIRM. Cohen and team used a portion of the cirmtuzumab antibody to construct ROR1 CAR T-cells. They discovered that ROR1 CAR T-cells were especially active in blood cancers, such as chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL) and acute lymphoblastic leukemia (ALL).

The award will allow the team to take the steps needed to finalize the clinical product and launch clinical trials to test ROR1 CAR T-cell safety and efficacy in patients with blood cancers. Since ROR1 is rarely found in normal adult tissues, the researchers expect their therapy to have minimal side effects.

“This really has the potential to provide a meaningful therapy to many patients with blood cancers that are resistant to standard chemotherapies, have few therapeutic options and dire prognoses,” said Cohen, who is also head of the Solid Tumor Therapeutics Program at Moores Cancer Center and co-director of the San Diego Center for Precision Immunotherapy. “These patients represent a tremendous, global unmet medical need.”

Shortly after an initial Phase I clinical trial, the researchers plan to expand their approach to address difficult-to-treat solid tumors, such as head and neck cancers, triple-negative breast cancer and pancreatic cancer, which also produce ROR1.

“CAR T-cell therapies represent a transformational advance in the treatment of hematologic malignancies,” said Maria T. Millan, MD, CIRM president and CEO. “This approach addresses the need to develop new therapies for patients whose cancers are resistant to standard chemotherapies, who have few therapeutic options and a very poor chance or recovery.

“Our goal is to always move the most promising research forward as fast as we can. That’s why these programs are so important. They reflect potential therapeutic approaches that have shown promise in the lab and are ready to take the next step, to undergo further testing and examination to see if they might be able to work in patients.”

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