Previous studies have explored the use of engineered blinatumomab-secreting autologous αβ T cells for CD19-targeted cancer therapy. To create a more flexible allogeneic delivery system, we utilized γ9δ2 T cells rather than αβ T cells in a similar application. First, we showed that γ9δ2 T cells could serve as effector cells for blinatumomab, and these effector memory cells could survive for at least 7 days after infusion. The genetically modified blinatumomab-secreting γ9δ2 T cells induced significant cytotoxicity in CD19⁺ tumor cell lines and primary cells from chronic lymphocytic leukemia patients. Of note, blinatumomab-secreting γ9δ2 T cells might also exhibit dual-targeting of CD19 and isopentenyl pyrophosphate, a universal tumor-associated antigen. Furthermore, blinatumomab-secreting γ9δ2 T cells killed CD19-transfected adherent cells, suggesting that the γ9δ2 T cells might be effective for treating solid tumors with appropriate cancer antigens. Together, these results demonstrate the promise of blinatumomab-secreting γ9δ2 T cells as a cancer therapy.

以前的研究探索了使用工程化的 blinatumomab 分泌自体 αβ T 细胞进行 CD19 靶向癌症治疗。为了创建更灵活的同种异体递送系统，我们在类似应用中使用了 γ9δ2 T 细胞而不是 αβ T 细胞。首先，我们发现 γ9δ2 T 细胞可以作为博纳吐单抗的效应细胞，这些效应记忆细胞在输注后至少可以存活 7 天。基因修饰的 blinatumomab 分泌 γ9δ2 T 细胞在 CD19 ^{+中诱导显着的细胞毒性}来自慢性淋巴细胞白血病患者的肿瘤细胞系和原代细胞。值得注意的是，分泌博纳吐单抗的 γ9δ2 T 细胞也可能表现出双重靶向 CD19 和异戊烯基焦磷酸盐，一种通用的肿瘤相关抗原。此外，分泌博纳吐单抗的 γ9δ2 T 细胞杀死了 CD19 转染的贴壁细胞，表明 γ9δ2 T 细胞可能有效治疗具有适当癌症抗原的实体瘤。总之，这些结果证明了 blinatumomab 分泌 γ9δ2 T 细胞作为癌症疗法的前景。