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Tuesday, Nov 28, 2023

Cancer Awareness & Prevention 2022 – Building on a History of Success Developing Novel Immunotherapies to Treat Cancer

Custom Content by the Los Angeles Business Journal

Cell-based therapies and immunotherapies are revolutionizing the fight against cancer and are being used in clinical settings to successfully treat patients with solid tumors as well as blood cancers.

UCLA Health’s cancer researchers are leading that charge — and have been for more than two decades.
Their groundbreaking research ushered the U.S. Food and Drug Administration’s approval of an immune checkpoint inhibitor as a first-line treatment for metastatic melanoma and non-small lung cancer. The drug now is being used globally, alone and in combinations with other drugs, to treat nearly two dozen types of cancer.

UCLA-led research also resulted in FDA approval of the first chimeric antigen receptor (CAR) T-cell therapy to treat resistant blood cancers. UCLA Health is one of the few hospitals in the U.S. to offer all five therapies.

“Now we have immunotherapy as a valid option for many patients with cancer,” said Antoni Ribas, MD, PhD, director of the Tumor Immunology Program at UCLA’s Jonsson Comprehensive Cancer Center and a member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA. “It effectively has given a fourth pillar of cancer therapy besides surgery, radiation therapy and chemical therapy.”

He noted many of today’s treatments stem from seminal discoveries made by researchers at UCLA in the mid-1990s – a time when generally accepted belief was that an immune response couldn’t be induced in cancer.

UCLA has long been a leader in bringing groundbreaking immunotherapies to market, such as with the 2014 approval of pembrolizumab (Keytruda) for metastatic melanoma, led and co-developed by Dr. Ribas.

Pembrolizumab works by blocking a protein called PD-1 that sits on the surface of immune cells and keeps them from recognizing and attacking cancer cells. This was the first class of PD-1 antibodies to receive FDA approval for the treatment of any cancer, ushering in a leading-edge approach that has proven to be game-changing in treating many different cancers.

Dr. Ribas’ work with immunotherapy didn’t end there; in 2017, he launched a first-of-its-kind clinical trial involving the use of genetically engineered blood stem cells to produce cancer-fighting T cells (the immune killer cells) to treat metastasized cancers that have a specific tumor marker, NY-ESO-1 — a protein produced by tumor cells such as melanoma and sarcoma. NY-ESO-1 is found in 10% to 20% of cancers.

One of Dr. Ribas’ current focuses is studying molecular imaging techniques, such as PET scans, to understand how novel immunotherapies work on a molecular level.
One of the more exciting breakthroughs in cancer treatments in the past five years has been in CAR T-cell therapies, which work by training a person’s immune system to fight cancer cells by genetically modifying their T cells to recognize and attack the cancer.

One of the first CAR T-cell therapies, axicabtagene ciloleucel (Yescarta), was approved in October 2017 to treat adults with relapsed or refractory diffuse large B-cell lymphoma. Arie Belldegrun, MD, director of the UCLA Institute of Urologic Oncology, was instrumental in commercially developing Yescarta. As founder and CEO of Kite Pharma, Dr. Belldegrun conducted the trials that led to the drug’s approval. UCLA Health was among the few hospitals to offer this therapy to patients.

Since then, UCLA has participated in clinical trials that have led to approval of additional CAR T-cell therapies, including brexucabtagene autoleucel (Tecartus), a CD19-directed therapy approved in 2020 to treat relapsed or refractory mantle cell lymphoma.
Trial co-investigator John Timmerman, MD, a professor of hematology/oncology in the David Geffen School of Medicine at UCLA, in April 2020 noted that after a year of follow-up, 61% of patients remained in remission.

Currently, five CAR T-cell therapies have been approved by the FDA to treat blood cancers — four types of lymphomas as well as multiple myeloma.
“CAR T-cell therapies have caused improvements in survival not seen in other therapies and truly raised the bar in the development of novel therapies,” said Sarah Larson, MD, assistant professor of hematology/oncology at the David Geffen School of Medicine at UCLA and the UCLA Jonsson Comprehensive Cancer Center.
Dr. Larson said while physicians now feel comfortable using the therapies, their goal moving forward is to find ways to improve them.

Learn more about UCLA Health at UCLAHealth.org.

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