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AACR 2015: Investigational CART-meso Immunotherapy Feasible for Patients With Advanced Cancers

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Key Points

  • Patients with advanced cancer were treated with their own T cells, which were modified to target mesothelin-expressing tumor cells.
  • Trial patients had no major adverse events, and the T cells were able to persist in the patients’ blood for up to 28 days.
  • Researchers plan to conduct studies to test CART-meso cells’ engraftment, persistence, bioactivity, and antitumor responses as well as to identify biomarkers of antitumor activity.

Patients with advanced cancers who received mesothelin-directed chimeric antigen receptor–modified T cells (CART-meso), a type of investigational adoptive immunotherapy, tolerated the treatment well, and there was evidence that the infused immune cells persisted in the patients’ blood circulation and successfully migrated to the patients’ tumor sites. These interim results from a phase I clinical trial were presented at the AACR Annual Meeting 2015, held April 18 to 22 in Philadelphia (Abstract CT105).

“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,”  said Janos L. Tanyi, MD, PhD, Assistant Professor of Gynecologic Oncology at the University of Pennsylvania.

Study Details

In this phase I study to evaluate the safety and feasibility of CART-meso cells in patients with mesothelin-expressing tumors, Dr. Tanyi and colleagues have enrolled five patients with advanced cancers (two with ovarian cancer, two with epithelial mesothelioma, and one with pancreatic cancer) so far. All patients underwent apheresis to isolate their T cells, which were then used to manufacture CART-meso cells. After this, the CART-meso cells were reinfused 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, and antitumor responses as well as to identify biomarkers of antitumor activity, according to Dr. Tanyi. Additionally, when tumor or body fluid 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 U.S. Food and Drug Administration guidelines, Dr. 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,” Dr. Tanyi noted.

“CAR T-cell technology is a promising arm of adoptive immunotherapy,” Dr. 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 supported by the Alliance for Cancer Gene Therapy, the Ovarian Cancer Research Fund, the National Cancer Institute SPORE, and Novartis.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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