Researchers at the UCLA Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research secured $4.6 million in grant money from the California Institute for Regenerative Medicine (CIRM). The grant will contribute to support a phase I clinical trial of a novel treatment for advanced sarcomas and other cancers with a specific tumor marker called NY-ESO-1.
The study will be used to test a therapeutic approach that genetically engineers each patient’s own blood-forming stem cells to produce cancer-fighting immune cells called T cells.
Led by UCLA’s Jonsson Comprehensive Cancer Center, the phase I clinical trial evaluates the safety and feasibility of administering NY-ESO-1 TCR (T cell receptor)engineered peripheral blood mononuclear cells (PBMC) and peripheral blood stem cells (PBSC) after a myeloablative conditioning regimen to treat patients with cancer that has spread to other parts of the body. The conditioning chemotherapy makes room in the patient’s bone marrow for new blood cells (PBMC) and blood-forming cells (stem cells) to grow. Giving NY-ESO-1 TCR PBMC and stem cells after the conditioning chemotherapy is intended to replace the immune system with new immune cells that have been redirected to attack and kill the cancer cells and thereby improve immune system function against cancer.
The interventional study will include 12 participants. The estimated study completion date is September 2022.
Engineering T cells with cancer-fighting receptors is already a promising area of cancer research. This method — known as adoptive T cell immunotherapy — typically involves collecting T cells from the circulating blood of patients with cancer, genetically engineering the T cells in the lab with a cancer-finding receptor and transfusing the modified cells back into the patient. This produces a short-term immune response that effectively reduces cancer cells. However, adoptive T cell immunotherapy has limitations: people with cancer might not have enough T cells for the approach to work and once transplanted back into patients, the number of modified T cells declines over time since they cannot self-renew and often the cancer recurs.
This trial will use positron emission tomography (PET) scanning, which is a noninvasive imaging technology that scans for diseases in the body and shows how organs and tissues are functioning. Each trial participant will undergo regular scans to track the engineered blood-forming stem cells and T cells to make sure the cells function as intended. If the cells behave abnormally, a drug can be administered to kill only the engineered cells. This part of the trial helps to ensure the safety of the patients.
This treatment platform is already being deployed in a related trial focused on multiple myeloma, which launched in September 2017 and is led by Ribas, who is also Director of the UCLA Parker Institute for Cancer Immunotherapy. That trial is funded by a $20 million grant from CIRM and support from the UCLA Broad Stem Cell Research Center. CIRM has been supporting Ribas’ work since 2008, beginning with a $3.07 million New Faculty Award that enabled him to develop the technology to deliver T cell receptor genes into blood-forming stem cells.
Directed by Dr. Theodore Scott Nowicki in collaboration with Dr. Antoni Ribas, the trial will test a therapeutic approach that genetically engineers each patient’s own blood-forming stem cells to produce cancer-fighting immune cells called T cells.
Sarcomas account for one percent of all adult cancers and 15 percent of all pediatric cancers diagnosed annually in the United States. They generally fit into one of two categories: soft tissue sarcomas, which begin in fat, muscle, nerves, blood vessels and other connective tissues; and osteosarcomas, which begin in bones and are often diagnosed in children, teenagers and young adults. Between 25 to 50 percent of sarcoma patients treated with conventional methods (surgery, radiation and chemotherapy) go on to develop metastatic disease, meaning the cancer spreads to other parts of the body. Patients with metastatic sarcoma have very few treatment options, none of which has been proven to increase survival.
“Sarcomas are difficult to treat because of their rarity and diversity–the cancer has more than 50 distinct subtypes,” said Nowicki, a fellow physician in the UCLA David Geffen School of Medicine division of pediatric hematology/oncology and a Pediatric Scientist Development Program Scholar. “Conventional treatments such as chemotherapies target tumors, and despite decades of research, a single therapy that works across all sarcoma subtypes has not been developed. Immunotherapies hold promise in treating this cancer because they can empower the immune system to fight many different subtypes of the disease.”