Removing roadblocks to tumor treatment

Nora Disis and colleagues find promise in expanded T-cell therapy for vaccinated cancer patients with advanced stage tumors
 Dr. Nora Disis (left) and Dr. Yushe Dang
Dr. Nora Disis (left), of the Clinical Research Division and University of Washington, and UW researcher Dr. Yushe Dang, have found the T-cell infusion process promising for their first patient. They hope to apply the therapy to patients with advanced-stage tumors who have relapsed following cancer-vaccine trials. By Stephanie Cartier

Adoptive T-cell therapy-a process that gives cancer patients' depleted immune systems an extra boost of T-cells-has been an effective treatment for certain viral diseases, and it's showing promise in other tumors such as melanoma. In a recent study, published in the March edition of Clinical Cancer Research, researchers from the Center and University of Washington found that adoptive T-cell therapy may also be of use in treating other tumors, such as breast and ovarian cancer.

Adoptive T-cell therapy requires investigators to harvest T-cells from patients, grow the cells in culture outside of the body, and infuse the cultured cells back into the patient, providing a surge of T-cell immunity. The treatment is easier in viral diseases as the number of viral-specific T-cells in the blood is high. Cancer patients present the challenge of fewer tumor-specific T-cells to find and harvest.

"Cancer-specific T-cells grow better when they are in a group, so isolating the very rare T-cell and trying to expand that single cell to great numbers has been one of the roadblocks to the clinical application of adoptive T-cell therapy," said Dr. Nora Disis, a professor of oncology at UW and a member of the Clinical Research Division.

One path around that roadblock has been to use a tumor-draining lymph node or the tumor itself as a source of T-cells specifically targeted to fight that tumor. However, access to these tissues can present obstacles, Disis said.

The researchers came upon a solution while looking for a vaccine to prevent disease relapse after cancer has been treated by standard therapy. Dr. Yushe Dang, of the UW, found that after vaccination, T-cells specific to the tumor were found in higher levels in the blood, and were much easier to grow outside the body than T-cells from unvaccinated patients.

The expansion of the T-cells takes about a month and then can be infused back into the patient for cancer treatment. Researchers believe this method of vaccine priming before T-cell harvest would be an effective and efficient way to generate T-cells for any tumor type. The team will use the strategy in a phase I clinical trial for vaccinated patients with advanced-stage tumors who no longer respond to standard therapies. To learn more, access the paper at http://clincancerres.aacrjournals.org/cgi/content/full/13/6/1883.

The funding for the study came from the National Cancer Institute and the Arnold and Mabel Beckman Foundation.

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