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David Geffen School of Medicine
 
The Cutting Edge

Wake-up Call

UCLA SCIENTISTS HAVE DISCOVERED a way to “wake up” the immune system to fight cancer by delivering an immune-system-stimulating protein directly into lung-cancer tumors. The new method harnesses the body’s natural defenses to fight disease growth.

The protein, CCL21, is delivered in a “vault,” barrel-shaped nanoscale capsules found in the cytoplasm of all mammalian cells. Preclinical studies in mice with lung cancer showed that the protein stimulated the immune system to recognize and attack cancer cells, potently inhibiting cancer growth, according to the study’s co-senior author Leonard Rome, Ph.D., a cell biologist at UCLA’s Jonsson Comprehensive Cancer Center and associate director of the California NanoSystems Institute at UCLA.

The goal of the research, Dr. Rome explains, was to alert the immune system, which has been suppressed in lung tumors, to the presence of the tumor cells, “to have the cancer say to the immune system, ‘Hey, I’m a tumor and I’m over here, come get me!’”

The study was published in the journal PLoS One.

The new vault-delivery system, which Dr. Rome characterized as “just a dream” three years ago, is based on a 10-year research effort. The research focused on using a patient’s white blood cells to create dendritic cells – immune-system cells that process antigens which, when presented to T cells, stimulate an immune response.

The vault nanoparticles containing the CCL21 have been engineered to slowly release the protein into the tumor over time, producing an enduring immune response. Although the vaults protect the packed CCL21, they act like a time-release capsule, Dr. Rome says.

If proven successful, the vault-delivery method would add a desperately needed weapon to the arsenal in the fight against lung cancer. “It’s crucial that we find new and more effective therapies to fight this deadly disease,” says Steven Dubinett, M.D., director of the Jonsson Comprehensive Cancer Center’s lung-cancer program. “Right now, we don’t have adequate options for therapies for advanced lung cancer.”

The researchers plan to test the vault-delivery method in human studies within the next three years. The vault nanoparticle would require only a single injection into the tumor because of the slow-release design, and it eventually could be designed to be patient-specific by adding the individual’s tumor antigens into the vault, Dr. Dubinett says.

 





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