A new study published today in The Journal for ImmunoTherapy of Cancer found that CAR T-cell therapy, a type of cancer treatment in which the immune system’s T cells are programmed to attack cancer cells, works well on mice with ovarian cancer.
The Karolinska Institutet researchers hope that their discovery will lead to a clinical trial to see how well the treatment works for women with the disease.
CAR T-cell treatment is a relatively new kind of immunotherapy that involves removing a patient’s immune cells (known as T cells) from their blood and infusing them with a new gene that targets a protein called a chimeric antigen receptor (CAR) on the surface of cancer cells. When reintroduced to patients, these T cells become more lethal, homing in on and destroying cancer cells.
“This therapy is currently available for patients with blood cancer,” says author Isabelle Magalhaes, “and we want to investigate if we can use the method to treat ovarian cancer.”
Despite several advances in treatment, the prognosis for women with ovarian cancer remains poor.
CAR T-cell therapy hasn’t worked very well against solid tumors until now.
Tumours often grow in places where T cells don’t do well, according to author Jonas Mattsson.
“This can cause attacking T cells to be neutralised, which impairs the therapeutic effect. So we wanted to examine if it would still work.”
Mesothelin is a protein found in many ovarian tumors, therefore the researchers decided to test three different CAR molecules that have been engineered to target it. As a result, they repeatedly exposed ovarian cancer cells to the programmed CAR T-cells in test tubes and carried out several mouse trials.
The M1xx subtype of CAR T cells proved to be the most effective, greatly extending the lifespan of the cancer-bearing mice compared to those in the control group. The tumor size was reduced and the mice who received injections of T cells that express that specific molecule lived even longer than the others. Even one or two of the mice got well.
“In several mice, there were no tumor cells left that we could detect, and the effect lasted just over three months after the treatment started,” adds Professor Mattsson.
“This is evidence that immunotherapy involving CAR T cells that attack the mesothelin protein is a promising one for ovarian cancer.”
He hopes that this finding will open the door to a clinical trial.
“Our goal is to predict the optimal conditions for producing CAR T cells able to infiltrate and attack the tumour and survive in the bodies of women with ovarian cancer.”
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