Mass Production of Patient-Specific Cancer-Targeting T Cells

Infusions of massive numbers of immune cells is a promising strategy for treating many conditions, as well as being something that would probably benefit any old person as a periodic compensation for the decline in the aging immune system. The technologies to enable this sort of therapy are falling into place:

Scientists have combined the ability to reprogram stem cells into T cells with a recently developed strategy for genetically modifying patients' own T cells to seek and destroy tumors. The result is the capacity to mass-produce in the laboratory an unlimited quantity of cancer-fighting cells that resemble natural T cells, a type of white blood cell that fights cancer and viruses. In a [recent study] researchers show that the genetically engineered cells can effectively wipe out tumors in a mouse model of lymphoma.

[Researchers] isolated T cells from the peripheral blood of a healthy female donor and reprogrammed them into stem cells. The researchers then used disabled retroviruses to transfer to the stem cells the gene that codes for a chimeric antigen receptor (CAR) for the antigen CD19, a protein expressed by a different type of immune cell - B cells - that can turn malignant in some types of cancer, such as leukemia. The receptor for CD19 allows the T cells to track down and kill the rogue B cells. Finally, the researchers induced the CAR-modified stem cells to re-acquire many of their original T cell properties, and then replicated the cells 1,000-fold.

"By combining the CAR technology with the iPS technology, we can make T cells that recognize X, Y, or Z. There's flexibility here for redirecting their specificity towards anything that you want." Yet questions remain about exactly what kind of cell the researchers created. [The researchers] used gene expression microarrays to compare the mRNA expression profiles of the engineered T cell precursors with several types of natural T cells from the female donor. The analysis revealed that the engineered cells more closely resemble the gd T cell subtype that is involved in an initial broad-spectrum immune response, rather than the αβ subtype, the so-called adaptive subtype, which is slower to respond, but retains a memory of its exposure to various antigens.



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