According to a story from MedCity News, a recent study revealed a potential weakness of CAR-T cell immunotherapies that reveals the need for precision and caution in the extraction process. CAR-T immunotherapy has been approved for the treatment of a variety of rare blood cancers, such as acute lymphoblastic leukemia and diffuse large B-cell lymphoma.
About CAR-T Cell Therapy
While CAR-T cell therapy is an innovative new breakthrough for treating these types of cancers, this study highlights a rare event that could render the therapy completely ineffective. CAR-T cell therapy works, more or less, by extracting a type of white blood cell called T-cells from the patient’s body. These cells are then modified in order to target a certain protein that is present in the cancerous cells found in the patient. After a brief period in which these modified cells are allowed to proliferate, they are then introduced back into the body of the patient. These modified cells are now able to target and destroy cancer cells.
A Fatal Mistake
In the study, a manufacturing error was made in which a cancerous B-cell was instead modified in the manner that is normally meant for the T-cells. In this instance, the treatment failed because the modified B-cell was able to avoid attack since the modification process masked the protein that the T-cells had been designed to target. The results were lethal: the patient experienced relapse and at the time of her death all of the cancer cells has become completely resistant to attack from CAR-T cells.
Could This Happen Today?
At the time of this incident, the therapy, now called Kymriah, was still in the developmental stage at the University of Pennsylvania. Generally, this risk of such a mishap is probably far lower now. As Kymriah is now a fully approved treatment on the market, the manufacturing tolerances for it are much stricter. Improvements in the drug extraction process have also made it less likely that a stray cancer cell could infiltrate the T-cell sample.
Still, the extraction process is not the same everywhere, with different hospitals often following their own protocols for this procedure. There is still a small risk that this issue could reappear, but Novartis, the developer of Kymriah, says that it has developed processes for filtering out B-cells, including those that are affected by cancer.