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.
"It gets complicated," said Dubinett, director of the Lung Cancer Program at UCLA's Jonsson Comprehensive Cancer Center, a professor of pathology and laboratory medicine, member of the California NanoSystems Institute and a co-senior author of the paper. "You have to have a confluence of things happen - the patient has to be clinically eligible for the study and healthy enough to participate, we have to be able to grow the cells and then genetically modify them and give them back."
There also was the challenge of patient-to-patient variability, said Sherven Sharma, a researcher at both the Jonsson Cancer Center and the California NanoSystems Institute, professor of pulmonary and critical care medicine and co-senior author of the study. It was easier to isolate and grow the dendritic cells in some patients than in others, so results were not consistent.
"We wanted to create a simpler way to develop an environment that would stimulate the immune system," Sharma said.
In the Phase I study, it takes more than a week to differentiate the white blood cells into dendritic cells and let them grow to the millions required for the therapy. The dendritic cells are infected with a virus engineered to carr
|Contact: Kim Irwin|
University of California - Los Angeles Health Sciences