PLos One - Novel CCL21-Vault Nanocapsule Intratumoral Delivery Inhibits Lung Cancer Growth
This study demonstrates that the vault nanocapsule can efficiently deliver CCL21 to sustain antitumor activity and inhibit lung cancer growth. The vault nanocapsule can serve as an “off the shelf” approach to deliver antitumor cytokines to treat a broad range of malignancies. Pre-clinical studies in mice with lung cancer showed that the protein stimulated the immune system to recognize and attack the cancer cells, potently inhibiting cancer growth.
This is related to earlier reports on nanoscale vaults for nanoparticle drug delivery at UCLA
The new vault delivery system, which Rome characterized as "just a dream" three years ago, is based on a 10-year, on-going research effort focusing on using a patient's white blood cells to create dendritic cells, cells of the immune system that process antigen material and present it on the surface to other immune system cells. A Phase I study that is part of the effort, led by ULCA's Dr. Steven Dubinett, used a replication-deficient adenovirus to infect the dendritic cells and prompt them to over-secrete CCL21, the first time the chemokine has been administered to humans. The engineered cells – 10 million at a time – were then injected directly into the patient's lung cancer to stimulate an immune response.
The early phase study has shown the dendritic cell method is safe, has no side effects and seems to boost the immune response – Dubinett and his team found T lymphocytes circulating in the blood stream with specific cytokine signatures, indicating that the lymphocytes were recognizing the cancer as a foreign invader.
However, the process to generate dendritic cells from the white blood cells and engineer them to over-secrete CCL21 is cumbersome, expensive and time-consuming. It also requires a Good Manufacturing Practice (GMP) suite, a specialized laboratory critical for the safe growth and manipulation of cells, which many research institutions do not have.
Rome, Dubinett and Sharma plan to test the vault delivery method in human studies within the next three years and hope the promising results found in the pre-clinical animal tumor models will be replicated. If such a study is approved, it would be the first time a vault nanoparticle is used in humans for a cancer immunotherapy.
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