Investigational “CART” Cells, A Personalized Cellular Cancer Therapy is Well Tolerated By Patients

Chimeric Antigen Receptor T cells or CART cells are genetically modified versions of a patients’ own immune cells that expressed molecules that specifically bind tumor cells and mark them for destruction.  A host of animal experiments have demonstrated the safety and effectiveness of CART cells for treating tumors, but getting a therapy to work in animals is different than getting it to work in human patients.


Thus, the recent news that patients treated with CART cells made from their own T cells are tolerating them well is very welcome news.  Equally welcome is the news that the infused CART cells successfully traveled to those tumors they were designed to attack in an early-stage trial for mesothelioma and pancreatic and ovarian cancers at the Perelman School of Medicine at the University of Pennsylvania. Data from these trials adds to an already growing body of research that shows that CAR T cell technology shows remarkable promise for fighting tumors.  These interim results will be presented at the American Association for Cancer Research (AACR) Annual Meeting 2015, April 18-22.

“The goal of this phase I trial was to study the safety and feasibility of CART-meso cells in patients with mesothelin-expressing tumors,” says Janos L. Tanyi, MD, PhD, an assistant professor of Gynecologic Oncology. “We found no major adverse events associated with the treatment, which suggests that the patients tolerated it very well. But importantly, the T cells successfully targeted the patients’ tumor sites and survived in the blood stream for up to 28 days.”

The data that Tanyi will present at this conference will consist of scans and measurements acquired from five different patients; two of whom are suffering from ovarian cancer, two who have epithelial mesothelioma, and one with pancreatic cancer.  All five patients agreed to received the new investigational CART cell therapy.  Significantly, all the patients who received this therapy had cancers that stopped responding to conventional treatments.

CAR T cells are made from each patient’s T lymphocytes that are extracted from blood by a process known as “apheresis.”  T lymphocytes are isolated from the blood cells by cell sorting and then genetically modified to secrete a special protein that identifies and attacks tumor cells.  In this case, the cells were genetically engineered to target those cancer cells that express a protein called Mesothelin on their surfaces.  The engineered protein secreted by the engineered T cells could identify and kill them the tumor cells.  Even though Mesothelin is also found on the surfaces of the pleura (membranes that surround the lungs), the peritoneum (the lining that surrounds the abdominal cavity), and the pericardium (the scar that surrounds the heart),a variety of tumors express Mesothelin at such high levels that they are much more likely to be attacked by the CAR T cells that the normal tissues.

The preliminary results suggest the T cells did not attack normal tissues, but these patients must be followed up annually for 15 years in order to more closely observe the persistence of the CART-meso cells, their potential antitumor activity, and to better characterize their safety profiles.  Because the CAR T cells to not last indefinitely in the bloodstream, their ability to attack normal tissue should, theoretically at least, be minimal.