Patients with advanced cancers who received chimeric antigen receptor- modified T cells (CART)-meso, a type of adoptive immunotherapy, tolerated the treatment well, and there was evidence that the injected immune cells persisted in the patients' blood circulation and successfully migrated to the patients' tumour sites, according to interim results from phase I clinical trial data presented at the AACR Annual Meeting 2015, April 18-22.
"CART cells are patients' own immune cells called T cells, modified to produce specific immunoreceptors, which can identify tumour cells that were not visible to the T cells previously. In this case, the T cells were modified to target tumour 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 Gynaecologic 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' circulation, and they successfully migrated to the patients' tumour sites. The interim results to date indicate that the therapy is safe in the patients treated so far," Tanyi added.
In this phase I study to evaluate the safety and feasibility of CART-meso cells in patients with mesothelin-expressing tumours, 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 patients received a single low dose of CART-meso cells without preconditioning chemotherapy.
The researchers will conduct studies to test CART-meso cells' engraftment, persistence, bioactivity, antitumour responses, and identify biomarkers of antitumour activity, according to Tanyi.
Additionally, when tumour or body fluids samples are available, the researchers will analyse mesothelin expression on tumour 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-tumour 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 tumour," Tanyi noted.
"CAR T-cell technology is one of the most promising arms 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."