$4.6M CIRM Grant to Fund Phase 1 Trial of New Immunotherapy for Advanced Sarcoma, Difficult-to-Treat Cancers

The California Institute for Regenerative Medicine (CIRM) has awarded a $4.6 million grant to researchers at the UCLA Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research for an ongoing Phase 1 clinical trial testing a new immunotherapy for advanced sarcoma and other hard-to-treat cancers.

The therapy involves genetically engineering the patient’s own blood-forming stem cells and mature T-cells, a type of immune cell commonly harnessed in immuno-oncology treatments, to make them target a specific tumor marker called NY-ESO-1.

The trial (NCT03240861) is recruiting participants who have metastatic (stage 4) cancer or a locally advanced cancer, unable to be removed with surgery, for which no other therapies with a survival benefit are available. The study is taking place at UCLA Jonsson Comprehensive Cancer Center; more information on contacts and locations is available here. 

This includes patients with sarcoma whose cancer has spread to other parts in the body — a complication that affects 25% to 50% of all sarcoma patients treated by conventional methods.

Sarcomas represent 1% of adult cancers and 15% of pediatric cancers in the U.S. They can be soft tissue sarcomas that start in the fat, muscle, nerves, blood vessels, and other connective tissues or osteosarcomas, which develop in bones and are most often are diagnosed in children and young adults.

“Sarcomas are difficult to treat because of their rarity and diversity — the cancer has more than 50 distinct subtypes,” Theodore Scott Nowicki, MD, a fellow doctor at the UCLA David Geffen School of Medicine and the trial’s director, said in a press release.

“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,” he added.

Nowicki will collaborate with Antoni Ribas, MD, PhD, also a professor at the UCLA David Geffen School of Medicine, who showed in prior trials that genetic modification of mature T-cells enables a short-term but immediate treatment against cancer.

Ribas is also a member of the UCLA Jonsson Comprehensive Cancer Center.

The Phase 1 trial will evaluate the safety and feasibility of a type of adoptive cell transfer (ACT), a rapidly emerging form of immunotherapy based on collecting and using patients’ own immune cells to treat their cancer.

Two types of cells will be collected from the patient’s blood: peripheral blood stem cells (PBSCs), which are able to continually supply all types of blood cells including T-cells; and mature T-cells, immune cells that can fight tumor cells.

In the laboratory, each of these cell populations will be genetically edited to express a T-cell receptor that recognizes NY-ESO-1, a protein that is highly produced in 10% to 20% of all cancers and 80% of synovial sarcomas, which affect the tissue around joints.

This protein is almost exclusively produced in tumor cells. So a receptor that specifically recognizes it redirects immune cells to attack and kill the cancer cells, sparing most of the others.

These engineered cells will be transplanted back into the patient, following a chemotherapy regimen to remove the patient’s blood cells and make room in the bone marrow for the new T-cells and stem cells to grow.

The approach is expected to work on two fronts, a short-term immediate action and a long-term, lasting immune response to the cancer.

Stem cells will differentiate into mature T-cells and provide an ongoing supply of T-cells programmed to recognize and kill NY-ESO-1-positive cancers.

But because it takes some time until mature T-cells can form from stem cells, the patient will also be infused with their own genetically modified mature T-cells. These cancer-fighting cells are ready for action and can buy time until the constant stem cell supply of mature T-cells begins to work.