“This therapy is currently available for patients with blood cancer, and we want to investigate whether we can use the method to treat ovarian cancer,” says Isabelle Magalhaes, associate professor of Oncology-Pathology at Karolinska Institutet and co-last author of the study. “Despite many improvements in available therapy, the prognosis for women with ovarian cancer is still poor.”
So far, CAR T-cell therapy has been shown to be ineffective against solid tumors.
Ovarian Cancer: New Findings
“Tumors often arise in an environment that is unfavorable for T cells, partly due to low oxygen levels,” says Jonas Mattsson, a professor at Karolinska Institutet and second co-author. “This can lead to neutralization of the attacking T cells, which weakens the therapeutic effect. So we wanted to test if it would still work.”
Many ovarian tumors contain mesothelin, and the researchers wanted to test three types of CAR molecules programmed to attack this particular protein. So they repeatedly exposed ovarian cancer cells to programmed CAR T-cells in test tubes and conducted several experiments on mice.
All three CAR T-cells significantly extended the life of cancer-bearing mice compared to mice in the control group, with M1xx CAR T-cells proving to be the most effective. Mice injected with T cells expressing that molecule saw a reduction in tumor size and lived longer than others. A few of the mice even recovered.
“In several mice, we had no detectable tumor cells left, and the effect lasted a little over three months after the start of treatment. This proves that immunotherapy involving CAR T cells that attack the mesothelin protein is promising for ovarian cancer,” – Professor Mattsson. he says.
“I hope this discovery will lead to clinical research,” he says. “Our goal is to predict the optimal conditions for the production of CAR T cells that can infiltrate and attack the tumor and survive in the body of women with ovarian cancer.”
The study was funded by a donation from the Swedish Cancer Society, the Swedish Childhood Cancer Foundation, the Radiumhemmet Cancer Research Foundation, the Swedish Research Council and Jeanette and Harald Mix.