Researchers at Medical University of South Carolina (MUSC) report that long-term expansion protocols for adoptive cancer immunotherapy does not compromise Th17 cells’ effectiveness against large tumors in the March 9.2017 issue of JCI insight. This is a significant finding 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 suggest that Th17 cell durability offers promise for next-generation ACT trials.
ACT is highly effective at activating the body’s immune defenses to fight against cancer. This immunotherapy involves extracting, expanding and enhancing the patient’s own T cells before returning them back to patient where they could induce a durable antitumor response.
In patients with metastatic melanoma treated with ACT, approximately 54% achieve an objective response and 24% achieve complete remission.
However, large infusion of T cells is required to produce successful antitumor responses. Rapid expansion protocols meet this need though it takes up to 3 months for enough tumor-reactive T cells to be produced in therapeutic dosages. Also, CD8+ T cells lose their potency quickly when they are extensively expanded outside the body.
For the first time, researchers have found that a subset of T cells- Th17 is resistant to expansion-induced degradation. It is found that Th17 cells withstand rapid expansion issues, has potent antitumor activity and provided a lucrative alternative to the CD8+ T cells that are traditionally used for ACT.
Uniqueness of Th17 cells:
Th17 cells could be expanded to large numbers without compromising their therapeutic quality. They have a natural propensity to expand without restimulation. Even when restimulated they do not impair the antitumor response as with CD8+ cells.
Since Th17 cells have stem-cell-properties and durability in mice, researchers hypothesized that they would retain their potent anti-tumor effectiveness after long-term expansion outside the body. Experiments showed that without any restimulation, Th17 cells robustly expanded for 21 days outside the body – producing around 5,000 time the original number of CD4+ cells to be returned to the patient.
However large amount of Th17 cells are required to eradicate large, aggressively growing tumors. Treatment with large quantities of Th17 cells obtained after 2-3weeks of expansion rapidly and completely eradicated these cancers in mice.
These findings play an important role for immunotherapy product development because Th17 cell durability provides a larger window for obtaining effective and potent T cells via expansion outside the body. They could also provide simplified clinical trial protocols-allowing preparation of ACT T cells easier for oncology centers around the world and providing the benefits of ACT for more patients.