Treating ovarian cancer with immunotherapy involving CAR T cells

Recent research published in The Journal for ImmunoTherapy of Cancer revealed that CAR T-cell therapy, a particular type of cancer treatment in which the immune system’s T cells are directed to kill tumor cells, is successful in treating ovarian cancer in mice.

Treating ovarian cancer with immunotherapy involving CAR T cells
Despite many improvements to the available therapy, the prognosis for women with ovarian cancer is still poor. Image Credit: Getty Images

The Karolinska Institutet researchers are hoping that the discovery may open the door for a clinical trial to determine how well the treatment works for women with the condition.

CAR T-cell therapy is a comparatively recent form of immunotherapy that entails removing immune cells from a patient’s blood (known as T cells) and infusing them with a new gene that selectively targets a protein known as a chimeric antigen receptor (CAR) on the surface of the cancer cells. The T cells are more aggressive when they are reintroduced to the patients, and they launch guided missile attacks on the cancer cells.

This therapy is currently available for patients with blood cancer, and we want to investigate if we can use the method to treat ovarian cancer. Despite many improvements to the available therapy, the prognosis for women with ovarian cancer is still poor.”

Isabelle Magalhaes, Study Joint Last Author and Docent, Department of Oncology-Pathology, Karolinska Institutet

Tumor environment unfavorable for T cells

CAR T-cell therapy has thus far been generally ineffectual against solid tumors.

Tumors often arise in an environment that’s unfavorable for T cells, in part due to a low oxygen level. This can cause attacking T cells to be neutralized, which impairs the therapeutic effect. So we wanted to examine if it would still work.”

Jonas Mattsson, Study Joint Last Author and Visiting Professor, Karolinska Institutet

Several ovarian tumors have mesothelin, and the investigators intended to test three different types of CAR molecules designed to target this specific protein. As a result, they constantly exposed ovarian cancer cells to the programmed CAR T-cells in test tubes and executed many mouse trials.

Mice lived longer

All three CAR T-cells dramatically extended the lifetimes of cancer-bearing mice compared to the control group, with M1xx CAR T cells proving the most effective. The mice that were treated with T cells that express that specific molecule had a smaller tumor and survived longer than the others. Many of the mice even recovered.

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. This is evidence that immunotherapy involving CAR T cells that attack the mesothelin protein is a promising one for ovarian cancer.”

Jonas Mattsson, Study Joint Last Author and Visiting Professor, Karolinska Institutet

What is the next stage of the research?

Jonas Mattsson says, “Hopefully, this discovery will pave the way for a clinical study. Our goal is to predict the optimal conditions for producing CAR T cells able to infiltrate and attack the tumor and survive in the bodies of women with ovarian cancer.”

Source:
Journal reference:

Schoutrop, E., et al. (2023) Tuned activation of MSLN-CAR T cells induces superior antitumor responses in ovarian cancer models. The Journal for ImmunoTherapy of Cancer. doi.org/10.1136/jitc-2022-005691.

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