Dr. Anderson on Overcoming Suppressive Signals by Engineering T-cells in Ovarian Cancer

Kristin G. Anderson, PhD, postdoctoral research fellow, Fred Hutchinson Cancer Research Center, University of Washington, discusses overcoming suppressive signaling by engineering T-cells in ovarian cancer.

Previous findings published in 2021 showed it is possible for patients to overcome suppressive signals that inhibit the activity of T cells by utilizing fusion receptors that combine an inhibitory receptor with an activating signal, Anderson says. Based on these findings, a fast 4-1BB fusion was developed that showed when combined in T cells with the new T-cell receptor. In a mouse model, T-cells combined with the 4-1BB fusion prolonged survival in the animals better than T cells with the receptor alone, Anderson explains.

The mechanism of the 4-1BB fusion increased persistence in the T cells. However, the T cells still lost function in the same way as T cells that only had the T-cell receptor, Anderson continues. Further research was undertaken to determine how to the T-cells could function better in the immunosuppressive tumor microenvironment, Anderson concludes.