MSCs plus TRAIL destroy metastatic lung cancer cells in mice.
Researchers at the University College of London (UCL) have demonstrated the ability of adult stem cells to deliver a cancer-killing protein to tumors.
Bone marrow mesenchymal stem cells (MSCs), used as vectors to transport anti-tumor therapy, carry TNF-related apoptosis-inducing ligand (TRAIL) to tumors, destroying the tumor cells while sparing normal cells. The genetically engineered stem cells are able to home to the cancer cells, both in culture and in mouse models. “Present oncological therapies are limited by host toxicity,” said Michael Loebinger, M.D., a researcher at UCL. “They are also limited by cancer resistance and may not destroy cancer stem cells.”
In this first study to intravenously introduce MSCs that have been genetically modified to deliver TRAIL, the investigators chose the breast cancer cells for both the culture and mouse models because in their in vitro experiments, the MSCs demonstrated a particularly strong homing to breast cancer cells. “Breast cancer tumors are a good model of metastases,” noted Dr. Loebinger, “but our plan is to test the engineered stem cells with other models, including lung cancer.”
In the study, presented May 19 at the American Thoracic Society’s 105th International Conference in San Diego, the scientists identified those cells likely to be resistant to therapies and found that they were just as likely to be destroyed as tumor cells by this novel therapy.
In culture, the stem cells caused lung, squamous, breast, and cervical cancer cells to die (all p< 0.01), even at low stem cell/tumor cell ratios (1:16). In mice, the researchers showed that the stem cells could reduce the growth of subcutaneous breast tumors by approximately 80% (p< .0001). The stem cells could also be injected intravenously as therapy for mice with lung metastases and could eliminate lung metastases in 38% of mice compared to control mice, all of which still had metastases (p=0.03).