Removing roadblocks to tumor treatment

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.