Immunotherapy, which involves reprogramming T-cells to find and attack cancer cells, is one of the fastest-growing areas of cancer research. One of the biggest challenges of immunotherapy is how to harness the power of T-cells against cancer without also turning them against healthy cells. A new study conducted in Switzerland and published in the Journal of Translational Medicine addressed the problem by reprogramming T-cells to recognize and attack mesothelioma cells that express a specific protein.
Fibroblast Activation Protein (FAP) is expressed on the surface of tumor-associated fibroblast cells which are found in the connective tissue of mesothelioma tumors. FAP is also found in mesothelioma cells and may play a role in the start of cancer, as well as the growth of the fibroblasts themselves. Because of FAP’s accessibility on the surface of cells, the Swiss team theorized that it might make a good target for cancer treatment.
First, the researchers confirmed the presence of FAP in mesothelioma cells by performing immunohistochemical evaluations on tumor samples from mesothelioma patients. All of the mesothelioma tumor samples tested expressed FAP. Just as significantly, FAP was not expressed by most of the healthy cells tested. Very weak FAP expression was detected in the pancreas, the placenta, the cervix and the uterus.
Next, researchers used an altered virus to give immune system cells (T-cells) an anti-FAP focus. When administered to laboratory mice, these redirected T-cells sought out and attacked FAP-expressing mesothelioma cells, shrinking tumors and prolonging survival. “FAP-specific re-directed T-cells inhibited the growth of FAP positive human tumor cells in the peritoneal cavity of mice and significantly prolonged survival of mice,” the authors write in a summary of their findings.
Although the approach appears promising, before it can be used in the treatment of human mesothelioma patients, it must undergo FDA clinical trials. The next step for anti-FAP immunotherapy would be Phase I trials to determine the safety and effectiveness of the approach and to determine the right dosing strategy. The authors of the new Swiss study say their data supports the need for a Phase I trial.
Schuberth, PC, et al, “Treatment of malignant pleural mesothelioma by fibroblast activation protein-specific re-directed T cells”, August 12, 2013, Journal of Translational Medicine.