Thursday 24 April, 2014

Genetically modified blood stem cells can help fight melanoma

Published On: Tue, Nov 29th, 2011 | Stem Cell Research | By BioNews

Blood stem cells can be genetically modified to create cancer-fighting cells and cure patients suffering from melanoma, a new study has suggested.

Researchers from UCLA’s cancer and stem cell centers believe this approach could be useful in 40 percent of Caucasians with this malignancy.

According to Jerome Zack, senior author of the study done in mouse models, the research is the first proof-of-principle that blood stem cells, which make every cell type found in blood, can be genetically altered in a living organism to create an army of melanoma-fighting T-cells.

“We knew from previous studies that we could generate engineered T-cells, but would they work to fight cancer in a relevant model of human disease, such as melanoma,” said Zack.

“We found with this study that they do work in a human model to fight cancer, and it’s a pretty exciting finding.”

Researchers used a T-cell receptor from a cancer patient cloned by other scientists that seeks out an antigen expressed by this type of melanoma.

They then genetically engineered the human blood stem cells by importing genes for the T-cell receptor into the stem cell nucleus using a viral vehicle.

Dimitrios N. Vatakis, study first author, said that the genes integrate with the cell DNA and are permanently incorporated into the blood stem cells, theoretically enabling them to produce melanoma-fighting cells indefinitely and when needed.

“The nice thing about this approach is a few engineered stem cells can turn into an army of T-cells that will respond to the presence of this melanoma antigen,” Vatakis said.

“These cells can exist in the periphery of the blood and if they detect the melanoma antigen, they can replicate to fight the cancer.”

In the study, the engineered blood stem cells were placed into human thymus tissue that had been implanted in the mice, which allowed the research 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 tumour that did not. The engineered cells specifically went after the antigen-expressing melanoma, leaving the control tumour 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.

Response was assessed not only by measuring physical tumour 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.

The study has been published in the Proceedings of the National Academy of Sciences.

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