Researchers from the Dartmouth Medical School recently conducted an investigation into the effects of using genetically modified T-cells, to combat multiple myeloma.. Amorette Barber, professor Kenneth Meehan and associate professor Charles Sentman found that this gene therapy was successful in treating myeloma in mice. Multiple myeloma is a form of cancer that affects specific white blood cells present in the bone. This study, conducted last year, was published in Nature this January.
As part of the treatment, T-cells, a type of white blood cell, were genetically modified to incorporate the protein chNKG2D. This protein is the binding site for a ligand – a molecule that attaches to a protein to trigger biological signals. This particular ligand is expressed by human myeloma tumor cells. This means the T-cells can target the myeloma cells specifically. In addition, upon contact, the T-cells containing chNKG2D can produce particular cytokines (molecules used for intracellular communication) that kill human myeloma cells.
It was found that this model worked in mice – the injected T-cells found and targeted the tumors present in the rodents, to great effect. Compared to a single dose of the regular or wild type T-cell, a single dose of the modified version ensured longer survival for half the sample tested, and a double dose led to tumor-free survival in all mice. In addition, the mice developed a protective memory response to the antigens produced by these specific myeloma cells, meaning their immune systems recognize this particular type of myeloma and a relapse is therefore unlikely.
It was also found that the introduction of these modified T-cells into the bodies of the mice did not require lymphodepletion – a process by which the number of T-cells and lymphocytes present in the body are reduced. This process normally accompanies T-cell infusions because it prolongs the life of the new T-cells. However, the chNKG2D T-cells do not live very long, potentially reducing the need for lymphodepletion. This short lifespan also suggests that the T-cells induce anti-tumor immune responses in the host system, essentially “teaching” the body how to respond to this specific form of myeloma. This is what makes the chance of relapse very low.
Multiple myeloma makes up roughly 10% of blood-related cancers, and causes 20% of the deaths due to these cancers in the United States. Many other forms of treatment, including stem cell transplants, have been used to combat multiple myeloma, but to little avail. While stem cell transplants have a high cure” rate, the rate of relapse is high too. The researchers also suggest that current chemotherapies for multiple myeloma are inadequate; they follow the same response pattern as the stem cell transplants – high response rates followed by high relapse rates.
Who knows, this novel form of gene therapy just might provide some answers.