IL-21 重编程的 Vδ1 T 细胞对实体瘤发挥杀伤作用并被 CAR 武装增强以用于现货型免疫治疗

Cancer cell therapies have primarily focused on engineering autologous T cells with chimeric antigen receptors (CARs), achieving clinical success against hematologic malignancies.

However, their effectiveness against solid tumors is limited by challenges such as antigen escape, suppression by the metabolically hostile tumor microenvironment (TME), and manufacturing difficulties. T cells are unconventional T cells with innate tumor-targeting capabilities independent of MHC class I, making them an emerging candidate for allogeneic cell therapy. While the V 1 T cell subset has shown promising anti-tumor killing their clinical application has been hindered by difficulties in achieving robust expansion for therapeutic use.

Here, we evaluated the potential of K562 feeder cells expressing membrane-bound IL-21 (K562-mb-IL-21) to expand and activate T cells from peripheral blood.

Our findings show that this method preferentially expands V 1 T cells, resulting in an activated phenotype characterized by enhanced expression of NK cell activation receptors, innate cytotoxicity against breast and ovarian cancer cells, and sustained metabolic function in patient-derived ascites TME. When engineered with a CAR, V 1 T cells exhibited further enhanced anti-tumor efficacy in an immunodeficient NRG xenograft model of human ovarian cancer.

These findings highlight K562-mb-IL-21 expanded peripheral blood V 1 T cells as a promising 'off-the-shelf' allogeneic therapy for solid tumors.