Philadelphia — In a recent issue of Cancer Research, Daniel J. Powell, Jr., PhD, a research assistant professor of Pathology and Laboratory Medicine and Obstetrics and Gynecology at the Perelman School of Medicine at the University of Pennsylvania, showed for the first time that engineered human T cells can eradicate deadly human ovarian cancer in immune-deficient mice. Ovarian cancer is the most lethal reproductive cancer for women, with one-fifth of women diagnosed with advanced disease surviving five years. Nearly all ovarian cancers (90%) are characterized by their expression of a distinct cell-surface protein called alpha-folate receptor, which can be a target for engineered T cells.

In a past clinical study, first generation engineered T cells did not shrink tumors in women with ovarian cancer because the T cells did not persist in the patients. The new second generation technology developed in the current study overcomes the limitations of the first generation approach. Here, second generation T cells shrank tumors; whereas, T cells engineered using first generation technology did not.

The alpha-folate receptor is expressed on the surface of ovarian cancer cells and has a high affinity for folic acid, a vitamin which helps "feed" the cancer cells, and represents an "Achilles' Heel" for cancer researchers to target.

"We anticipate the opening of a genetically modified T cell clinical trial in the next few months for women with recurrent ovarian cancer," says Powell. "Targeting the alpha-folate receptor is an opportunity for widespread clinical application."

Until now, human T cells engineered to express an antibody fragment specific for the alpha-folate receptor protein have shown anti-tumor activity against epithelial cancers in the lab, but not in the clinic due to their inability to persist and home to tumors in the human body. The modified T cells used in this study express an engineered fusion protein – called a chimeric antigen receptor — that combines the specificity of an antibody with the T cell signaling portions from two different proteins that stimulate the immune system to recognize ovarian cancer cells. These added signaling protein pieces give the engineered T cells the extra survival signals they need to do their job.

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