Th17 Cells Do Not Lose Anti-Tumor Potency When Expanded Outside Body: New Findings in Mouse Model Have Implications for Advancing Field of Cancer Immunotherapy

In the March 9, 2017 issue of JCI Insight, Medical University of South Carolina (MUSC) investigators report that long-term expansion protocols for adoptive cancer immunotherapy do not compromise Th17 cells' effectiveness against large tumors. This finding is important because rapid expansion protocols (REPs) that are used to produce sufficient CD8+ T cell numbers for adoptive cell therapy (ACT) degrade their effectiveness. These findings underscore that Th17 cell durability offers promise for next-generation ACT trials. ACT is highly effective at activating the body's immune defenses to fight cancer. This immunotherapy involves extracting, expanding, and enhancing the patient's own T cells before returning them to the patient where they can induce a durable anti-tumor response. In fact, among metastatic melanoma patients treated with ACT, approximately 54 percent achieve an objective response and 24 percent achieve complete remission. However, infusion of large numbers of T cells is required to produce successful anti-tumor responses. Rapid expansion protocols meet this need, but take up to three months before enough tumor-reactive T cells are available to effectively treat cancer patients. In addition, the CD8+ T cells commonly used in clinical trials quickly lose potency when they are extensively expanded outside the body. The open-access JCI Insight article is titled “Th17 Cells Are Refractory to Senescence and Retain Robust Antitumor Activity After Long-Term Ex Vivo Expansion.” Preclinical studies by an MUSC research team led by Chrystal Paulos, Ph.D., Associate Professor of Microbiology and Immunology and Endowed Peng Chair of Dermatology and including Medical Scientist Training Program (MSTP) student Jacob Bowers, demonstrate for the first time that one T cell subset, Th17 cells, is resistant to expansion-induced degradation.
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