Dr. Steven Dubinett

New grant funds cutting-edge UCLA clinical trial for late-stage lung cancer

By Mirabai Vogt-James | May 24, 2018 Clinical Trials

Scientists at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA have been awarded a $12M grant from the California Institute for Regenerative Medicine – also known as CIRM – to initiate a phase 1 clinical trial to test a novel cancer treatment for advanced-stage lung cancer. The treatment will combine an immunotherapy drug called pembrolizumab with injections of the patient’s own genetically modified immune cells directly into lung cancer tumors. Directed by Dr. Steven Dubinett, the goal of the trial is to use this combined approach to activate a targeted and precise immune response against lung cancer.

Approximately 85 percent of people with lung cancer succumb to the disease within five years of diagnosis, in part because the cancer is often detected at an advanced stage that only partially responds to current available treatments.

“New immunotherapy drugs such as pembrolizumab are effective for approximately 20 percent of lung cancer patients, so new options are needed for combination therapies that improve these results,” said Dubinett, a professor of medicine, chief of the Division of Pulmonary and Critical Care Medicine at the UCLA David Geffen School of Medicine and a member of the UCLA Broad Stem Cell Research Center.

The new clinical trial will combine pembrolizumab, an FDA-approved immunotherapy, with a special category of immune cells called dendritic cells injected into lung cancer tumors. Dendritic cells utilized in the trial will be generated from unique stem-cell-like blood cells drawn from each patient; this means that the cellular therapy will be perfectly matched to every patient.

Dendritic cells help a different category of immune cells – T cells – combat cancer as well as foreign invaders such as bacteria, viruses and toxins. Because they are able to migrate into cancer tumors, dendritic cells can capture and transfer information from cancer cells within the tumor to the surface of the dendritic cell. This makes the information visible to T cells, which then recognize and bind to the information and activate an immune response against the cancer. But this natural immune response isn’t typically enough to fight cancer on its own because T cells aren’t able to get inside tumors. To address this challenge, the dendritic cells used in the trial will be genetically modified with a molecule called CCL21, which will attract T cells into the tumor.  

Injecting patients’ lung cancer tumors with their own dendritic cells carrying the CCL21 molecule has already been tested in a previous clinical trial under Dubinett’s direction. That trial showed that dendritic cells expressing CCL21 triggered T cells to migrate into lung cancer tumors. However, the trial also found that the tumor cells increased levels of a protein called PD-L1, which inhibits T cell activity. Since pembrolizumab reactivates T cells against cancer by blocking their interaction with PD-L1, Dr. Dubinett and his team concluded that combining the drug with dendritic cell injections may be the key to a more effective treatment strategy.

“Our new trial will combine two treatments that have shown promise but have not been effective enough on their own,” said Dubinett, who is also a member of the UCLA Jonsson Comprehensive Cancer Center. “We anticipate that this combined therapy will create a beneficial response for more patients with lung cancer.”

In collaboration with Dr. Dubinett’s UCLA colleague, Dr. Edward Garon, an associate professor of medicine, trial participants will receive pembrolizumab plus three injections of the CCL21 dendritic cells directly into their lung cancer tumors. The dendritic cell injections will occur over a span of 42 days, and pembrolizumab will be administered for up to a year after the initial treatment.

The trial, also supported by the UCLA Broad Stem Cell Research Center and the CIRM-funded UCLA-UCI Alpha Stem Cell Clinic, has received approval from the U.S. Food and Drug Administration to begin enrolling patients.

If you think you might be eligible to enroll, please contact Research Assistant Benjamin Jones by email at benjaminjones@mednet.ucla.edu or by phone at (310) 453-2183.

Cancer & Immunotherapy Heart & Lung Diseases