A strategy to reconstitute immunity without GVHD via adoptive allogeneic Tscm therapy

作者：Liping Guan, Yunqin Sun, Yifan Si, Qingya Yan, Ziyu Han, Youxun Liu, Tao Han · 发表于：Frontiers in Immunology · 年份：2024 · DOI：10.3389/fimmu.2024.1367609 · 被引用次数：1 · 研究领域：CAR-T cell therapy research、Immune Cell Function and Interaction、T-cell and B-cell Immunology

Introduction: Adoption of allogeneic T cells directly supplements the number of T cells and rapidly induces T-cell immunity, which has good efficacy for treating some tumors and immunodeficiency diseases. However, poor adoptive T-cell engraftment and graft-versus-host disease (GVHD) limit the application of these methods. Alloreactive T-cell clones were eliminated from the donor T-cell repertoire, and the remaining T-cell clones were prepared as Tscm for T-cell adoptive treatment to reconstruct recipient T-cell immunity without GVHD. Methods: The subjects in this study included three different strains of mice. Lymphocytes from mice (C57BL/6) were used as the donor T-cell repertoire, from which the Tscm allo-reactive T cell clone was depleted (ATD-Tscm). This was confirmed by showing that the Tscm was not responsive to the alloantigen of the recipient (BALB/c). To prepare ATD-Tscm cells, we used recipient lymphocytes as a simulator, and coculture of mouse and recipient lymphocytes was carried out for 7 days. Sorting of non-proliferative cells ensured that the prepared Tscm cells were nonresponsive. The sorted lymphocytes underwent further expansion by treatment with TWS119 and cytokines for an additional 10 days, after which the number of ATD-Tscm cells increased. The prepared Tscm cells were transferred into recipient mice to observe immune reconstitution and GVHD incidence. Results: , effectively recognizing and answering the "foreign" antigen without causing GVHD after they...