In vitro expansion of stem-like memory T cells via D-mannose supplementation.

The therapeutic success of adoptive T cell therapy (ACT) is closely tied to the in vivo persistence and differentiation state of transferred T cells. Clinical evidence consistently shows that less differentiated T cells, particularly memory T cells with stem-like properties, offer superior antitumor activity and long-lasting immune responses. However, these stem-like memory T cells are challenging to expand efficiently using conventional in vitro culture protocols. Existing strategies, such as brief CD3/CD28 antibodies co-stimulation combined with cytokines like IL-7, IL-15, and IL-21, have shown limited success but remain costly and operationally complex, hindering scalability for clinical use. There is a critical need for a rapid, efficient, cost-effective, and clinically viable method to induce and expand this T cell subset. Here, we present an optimized mannose-based culture approach that enables robust in vitro expansion of stem-like memory T cells, offering a practical solution to current limitations and paving the way for improved ACT applications.