Scientists Managed To Create Engineered Cancer-Killing T-Cells That Target Melanoma
Scientists from University of California – Los Angeles have managed to determine stem cell to differentiate into a type of engineered T-cells that target cancer cells in human model patients suffering from melanoma. These cancer killing T-cells could hep about 40 percent of Caucasian patients that are experiencing this awful disease.
Previous studies have demonstrated that human stem cells can be determined to differentiate after genetic alteration, into melanoma fighting T-cells in mouse models.
Jeroma Zack, senior author and his team now tried to prove that engineered T-cells have the ability to attack cancer cells in a relevant model of human disease – melanoma . The researchers discovered that the engineered cells have functioned as designed, attacking cancer cells. The study was published in the online edition of Proceedings of the National Academy of Sciences journal.
Every cell in the human body posses its own type of antigens, and for this study researchers used a cloned T-cell receptor that binds with a particular melanoma cancer cell antigen. Afterwards, they modified the blood stem cells by inserting in their nucleus genes that code the T-cell receptor using a viral vector. The genes are incorporated in the stem cells DNA enabling them to be able to differentiate into cancer-fighting cells only when needed. The best part is that only a small part of the engineered stem cell can differentiate into specific cancer fighting T-cells when they sense the presence of the melanoma antigen. These type of genetically modified stem cells can remain dormant in the blood periphery and only start to replicate when melanoma antigen stimulates them.
During the research, the engineered blood stem cells were injected into a human thymus ( the body’s site of T-cell differentiation) and then implanted in mice. This approach made possible studying the human immune system response to cancer using a living model. After 6 weeks, the genetically modified stem cells differentiate into specific melanoma T-cells that started to attack the desired cancerous cells. Furthermore, the mice were implanted two different types of melanoma, one with the specific antigen that stimulates the genetically modified T-cells to differentiate and one melanoma type that did not. The genetically modified cells were attracted only by the cancer type that expressed the specific antigen; the control tumor remained untouched.
The study was conducted on nine mice, in four subjects the melanomas that presented the expression of the specific antigen were completely disposed. In the remaining five mice, a significant decrease of tumor size was noticed.
The results are quite promising as scientists now hope to be able to genetically modify stem cells to differentiate into engineered T-cells that coud fight different types of cancers like breast cancer or prostate cancer. The the downside is that their function is not a long-term one and more and more engineered T-cells need to be produced to sustain this kind of immune response. One possible solution would be engineering both the peripheral T-cells and the blood stem cells lines to differentiate into this king of cancer seeking T-cells.