“CAR T cells are patients’ own immune cells called T cells, modified to produce specific immunoreceptors, which can identify tumor cells that were not visible to the T cells previously. In this case, the T cells were modified to target tumor cells that express a protein called mesothelin on their surface [hence the name CART-meso], so that the T cells can identify them and kill them,” said Janos L. Tanyi, MD, PhD, an assistant professor in the Division of Gynecologic Oncology at the University of Pennsylvania in Philadelphia.
“We treated a small group of patients with advanced cancers and found no major adverse events associated with the T-cell infusion, suggesting that the patients tolerated the treatment very well. In addition, the modified T cells were able to persist for up to 28 days in the patients’ blood, and they successfully migrated to the patients’ tumor sites,” Tanyi added.
In this phase I study to evaluate the safety and feasibility of CART-meso cells in patients with mesothelin-expressing tumors, Tanyi and colleagues have enrolled five patients with advanced cancers (two with serous ovarian cancer, two with epithelial mesothelioma, and one with pancreatic cancer) so far. All patients underwent a procedure called apheresis to isolate their T cells, which were then used to manufacture CART-meso cells. After this, the CART-meso cells were re-infused into the patients. All of the patients received a single infusion of CART-meso cells without preconditioning chemotherapy.
The researchers plan to conduct studies to test CART-meso cells’ engraftment, persistence, bioactivity, antitumor responses, and identify biomarkers of antitumor activity, according to Tanyi. Additionally, when tumor or body fluids samples are available, the researchers will analyze mesothelin expression on tumor cells and CART-meso trafficking. Patients will be followed annually for up to 15 years in accordance with the FDA guidelines, Tanyi said.
“We did not see off-tumor on-target toxicity, which in this case would be an adverse event on normal tissues such as pleura or peritoneum. This means that the T cells did not attack the normal tissues that express mesothelin. Instead they migrated to the tumor,” Tanyi noted.
“CAR T-cell technology is a promising arm of adoptive immunotherapy,” Tanyi said. “Our long-term goal is to develop a new generation of CART-meso cells that can persist in the patients for years so that, besides eliminating cancer cells, they could also prevent recurrence of the disease.”
This study was funded by The Joan Miller and Linda Bernstein Ovarian award from the Alliance for Cancer Gene Therapy, the Ovarian Cancer Research Fund, the National Cancer Institute SPORE, and Novartis. Tanyi declares no conflicts of interest.
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