Adoptive T cell therapy proves effective in preclinical study; strategy to be evaluated in clinical trials
BUFFALO, N.Y. — Adoptive T cell therapy, which involves the expansion and infusion of a patient’s own immune cells, has emerged as a promising treatment for patients with metastatic melanoma. But efforts to apply these advances clinically have been limited by difficulties in obtaining long-lasting T cells that can survive following infusion. A team of researchers from Roswell Park Comprehensive Cancer Center, the University of Michigan and Kyoto University has reported significant progress in this area, achieving the first successful generation of pluripotent stem cells from melanoma-targeting T cells in a preclinical study, results of which have been published in the Cancer Research, a journal of the American Association for Cancer Research.
Induced pluripotent stem (iPS) cells — adult cells reprogrammed to function like embryonic stem cells — hold great promise in the field of regenerative medicine because they are long-lasting, can be made to differentiate into a wide range of tissues, and can be stored for use in generating an unlimited number of patient-specific T cells for use in cancer immunotherapy.
A team led by Fumito Ito, MD, PhD, Assistant Professor of Oncology in the Department of Surgical Oncology at Roswell Park, established a preclinical model for developing and evaluating these iPS cell-derived T cells. The authors report that these adoptively transferred iPS cell-derived T cells evaded immune rejection; mediated regression of large tumors; improved survival of the lab models studied; and established antigen-specific immunological memory, suggesting that this therapeutic approach could be effective long-term. This latest work developed concepts explored in an earlier study, first reported in 2015 in the journal Stem Cells International, in which Dr. Ito and colleagues demonstrated that iPS cells can be generated from T cells within human melanoma tumors.
“Our findings are highly encouraging, and we expect that this work will provide the foundation for developing personalized, immune-based therapies for patients with advanced and metastatic melanoma,” says Dr. Ito, who also holds a faculty appointment with the Roswell Park Center for Immunotherapy. “We plan to further develop this strategy using T cells derived from engineered iPS cells, and looking not only at melanoma but at other types of cancer.”
The work was funded, in part, by institutional funds from the University of Michigan and Roswell Park Comprehensive Cancer Center and by grants from the Central Surgical Association, American College of Surgeons, Melanoma Research Alliance, National Cancer Institute (project no. K08CA197966) and National Center for Advancing Translational Sciences (project no. UL1TR000433).
The paper, “Adoptive transfer of CD8+ T cells generated from induced pluripotent stem cells triggers regressions of large tumors along with immunological memory,” is available at cancerres.aacrjournals.org. Dr. Ito will present updated findings from this study at the annual meeting of the American Association of Immunologists, to be held May 13-17 in Seattle, Wash.
The mission of Roswell Park Comprehensive Cancer Center is to understand, prevent and cure cancer. Founded in 1898, Roswell Park is one of the first cancer centers in the country to be named a National Cancer Institute-designated comprehensive cancer center and remains the only facility with this designation in Upstate New York. The Institute is a member of the prestigious National Comprehensive Cancer Network, an alliance of the nation’s leading cancer centers; maintains affiliate sites; and is a partner in national and international collaborative programs. For more information, visit www.roswellpark.org, call 1-800-ROSWELL (1-800-767-9355) or email AskRoswell@Roswellpark.org. Follow Roswell Park on Facebook and Twitter.
Annie Deck-Miller, Senior Media Relations Manager