肿瘤细胞治疗研究
英文原题：CD4(+) anti-TGF-β CAR T cells and CD8(+) conventional CAR T cells exhibit synergistic antitumor effects.
这些发现提示，在 CD4 + T 细胞中用 T28zT2 重塑 TGF- 信号通路是清除实体瘤的一种有前景的策略。
转化生长因子（TGF）-β1 会限制 CD4⁺ T 细胞的扩增、存活和功能。研究显示，抗 TGF-β 的 CD4⁺ CAR-T 细胞（T28zT2 T 细胞）可抑制肿瘤生长，而抗 TGF-β 的 CD8⁺ T 细胞不能；这一作用部分通过分泌颗粒酶 B 和干扰素（IFN）-γ 实现。经 TGF-β1 处理的 CD4⁺ T28zT2 T 细胞在外周血和肿瘤中持续存在，维持线粒体形态与功能，且不会造成体内毒性。这些细胞还能在体内改善未转导 CD8⁺ T 细胞的扩增和持久性。肿瘤浸润的 CD4⁺ T28zT2 T 细胞富集表达 TCF-1⁺、IL7R⁺ 的记忆样 T 细胞，表达 NKG2D，并下调包括 PD-1 和 LAG3 在内的 T 细胞耗竭标志物。重要的是，CD4⁺ T28zT2 T 细胞与靶向磷脂酰肌醇蛋白聚糖 3（GPC3）或间皮素（MSLN）的 CD8⁺ CAR-T 细胞联合，在异种移植模型中显示增强的抗肿瘤作用。这些发现提示，在 CD4⁺ T 细胞中通过 T28zT2 重构 TGF-β 信号，是清除实体瘤的一种有前景策略。
Transforming growth factor (TGF)- 1 restricts the expansion, survival, and function of CD4 + T cells. Here, we demonstrate that CD4 + but not CD8 + anti-TGF- CAR T cells (T28zT2 T cells) can suppress tumor growth partly through secreting Granzyme B and interferon (IFN)- . TGF- 1-treated CD4 + T28zT2 T cells persist well in peripheral blood and tumors, maintain their mitochondrial form and function, and do not cause in vivo toxicity. They also improve the expansion and persistence of untransduced CD8 + T cells in vivo. Tumor-infiltrating CD4 + T28zT2 T cells are enriched with TCF-1 + IL7R + memory-like T cells, express NKG2D, and downregulate T cell exhaustion markers, including PD-1 and LAG3. Importantly, a combination of CD4 + T28zT2 T cells and CD8 + anti-glypican-3 (GPC3) or anti-mesothelin (MSLN) CAR T cells exhibits augmented antitumor effects in xenografts. These findings suggest that rewiring TGF- signaling with T28zT2 in CD4 + T cells is a promising strategy for eradicating solid tumors.
MEMBER ACCOUNT
登录成功会直接打开下一页。
