On November 23, 2021 the California Institute for Regenerative Medicine (CIRM) The board approved a $ 4.1 million grant to enable researchers at the University of California San Diego School of Medicine to bring a new T-cell therapy with chimeric antigen receptors (CAR) from the lab to the clinic .
In this cancer therapy, the patient’s own T cells, a type of immune cell, are obtained from a blood sample and genetically modified in the laboratory so that they can recognize proteins on tumor cells. Once infused into the patient, the CAR T cells kill the targeted cancer cells.
The work is directed by the main examiner Ezra Cohen, MD, Professor at UC San Diego School of Medicine, Associate Director of Clinical Science and Head of the Department 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 Moore’s Cancer Center.
In previous laboratory studies, Cohen and his team developed CAR T cells that specifically target ROR1, a molecule found on the surface of many cancer cells. ROR1 is normally only used by embryonic cells during early development, but can also be used by cancer cells to promote tumor growth.
ROR1 is also the target of cirmtuzumab, an experimental monoclonal antibody-based drug developed by another research team at the UC San Diego School of Medicine with funding from the CIRM. Cohen and his team used a portion of the cirmtuzumab antibody to construct ROR1-CAR T cells. They discovered that ROR1-CAR T cells were particularly active in blood cancers such as chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL) and acute lymphoblastic leukemia (ALL).
The award will enable the team to take the necessary steps to finalize the clinical product and start clinical trials to test the safety and efficacy of ROR1 CAR-T cells in blood cancer patients. Since ROR1 is rarely found in normal adult tissues, the researchers expect minimal side effects from its therapy.
“This really has the potential to provide useful therapy for many blood cancer patients who are resistant to standard chemotherapy, with few therapeutic options and poor prognoses,” said Cohen, who is also the director of the Solid Tumor Therapeutics Program at Moores Cancer Center is and co-director of the San Diego Center for Precision Immunotherapy. “These patients represent a tremendous global unmet medical need.”
Soon after an initial Phase I clinical trial, the researchers plan to expand their approach to hard-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 transformative advancement in the management of hematologic malignancies,” said Maria T. Millan, MD, President and CEO of CIRM. “This approach addresses the need to develop new therapies for patients whose cancer is resistant to standard chemotherapy, who have few therapeutic options and have very poor chance or recovery.
“Our goal is to always move the most promising research forward as quickly as possible. That is why these programs are so important. They reflect potential therapeutic approaches that have shown promise in the laboratory and are ready to take the next step of undergoing further testing and research to see if they could work in patients. “
CIRM was founded in 2004 by California voters to fund stem cell research in the state with the goal of expediting treatment for patients with unmet medical needs. The agency funds research at institutions and companies across California. In 2020, California voters approved further funding for CIRM.