In the study, the engineered blood stem cells were placed into human thymus tissue that had been implanted in the mice, allowing Zack and his team to study the human immune system reaction to melanoma in a living organism. Over time, about six weeks, the engineered blood stem cells developed into a large population of mature, melanoma-specific T-cells that were able to target the right cancer cells.
The mice were then implanted with two types of melanoma, one that expressed the antigen complex that attracts the engineered T-cells and one tumor that did not. The engineered cells specifically went after the antigen-expressing melanoma, leaving the control tumor alone, Zack said.
The study included nine mice. In four animals, the antigen-expressing melanomas were completely eliminated. In the other five mice, the antigen-expressing melanomas decreased in size, Zack said, an impressive finding.
Response was assessed not only by measuring physical tumor size, but by monitoring the cancer's metabolic activity using Positron Emission Tomography (PET), which measures how much energy the cancer is "eating" to drive its growth.
"We were very happy to see that four tumors were completely gone and the rest had regressed, both by measuring their size and actually seeing their metabolic activity through PET," Zack said.
This approach to immune system engineering has intriguing implications, Zack said. T-cells can be engineered to fight disease, but their function is not long-lasting in most cases. More engineered T-cells ultimately are needed to sustain a response. This approach engineers the cells that give rise to the T-cells, so "fresh" cancer-killing cells could be generated when needed, perhaps protecting ag
|Contact: Kim Irwin|
University of California - Los Angeles Health Sciences