Prussian blue nanoparticle-based photothermal therapy (PBNP-PTT) is an effective tumor treatment capable of eliciting an antitumor immune response. Motivated by the ability of PBNP-PTT to potentiate endogenous immune responses, we recently demonstrated that PBNP-PTT could be used ex vivo to generate tumor-specific T cells against glioblastoma (GBM) cell lines as an adoptive T cell therapy (ATCT). In this study, we further developed this promising T cell development platform. First, we assessed the phenotype and function of T cells generated using PBNP-PTT. We observed that PBNP-PTT facilitated CD8+ T cell expansion from healthy donor PBMCs that secreted IFNγ and TNFα and upregulated CD107a in response to engagement with target U87 cells, suggesting specific antitumor T cell activation and degranulation. Further, CD8+ effector and effector memory T cell populations significantly expanded after co-culture with U87 cells, consistent with tumor-specific effector responses. In orthotopically implanted U87 GBM tumors in vivo, PBNP-PTT-derived T cells effectively reduced U87 tumor growth and generated long-term survival in >80% of tumor-bearing mice by Day 100, compared to 0% of mice treated with PBS, non-specific T cells, or T cells expanded from lysed U87 cells, demonstrating an enhanced antitumor efficacy of this ATCT platform. Finally, we tested the generalizability of our approach by generating T cells targeting medulloblastoma (D556), breast cancer (MDA-MB-231), neuroblastoma (SH-SY5Y), and acute monocytic leukemia (THP-1) cell lines. The resulting T cells secreted IFNγ and exerted increased tumor-specific cytolytic function relative to controls, demonstrating the versatility of PBNP-PTT in generating tumor-specific T cells for ATCT.

中文翻译：

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光热普鲁士蓝纳米颗粒可产生有效的多靶点肿瘤特异性 T 细胞作为过继细胞疗法

基于普鲁士蓝纳米颗粒的光热疗法（PBNP-PTT）是一种有效的肿瘤治疗方法，能够引发抗肿瘤免疫反应。受 PBNP-PTT 增强内源性免疫反应能力的启发，我们最近证明 PBNP-PTT 可用于离体产生针对胶质母细胞瘤 (GBM) 细胞系的肿瘤特异性 T 细胞，作为过继性 T 细胞疗法 (ATCT)。在这项研究中，我们进一步开发了这个有前景的 T 细胞开发平台。首先，我们评估了使用 PBNP-PTT 生成的 T 细胞的表型和功能。我们观察到，PBNP-PTT 促进健康供体 PBMC 的 CD8+ T 细胞扩增，这些 PBMC 分泌 IFNγ 和 TNFα，并上调 CD107a 以响应与靶 U87 细胞的接触，表明特异性抗肿瘤 T 细胞激活和脱颗粒。此外，与 U87 细胞共培养后，CD8+ 效应和效应记忆 T 细胞群显着扩增，与肿瘤特异性效应反应一致。在体内原位植入的 U87 GBM 肿瘤中，PBNP-PTT 衍生的 T 细胞有效地减少了 U87 肿瘤的生长，并在第 100 天时使 >80% 的荷瘤小鼠实现了长期存活，而用 PBS 治疗的小鼠只有 0% 存活。非特异性 T 细胞，或从裂解的 U87 细胞中扩增的 T 细胞，证明了该 ATCT 平台增强的抗肿瘤功效。最后，我们通过生成针对髓母细胞瘤 (D556)、乳腺癌 (MDA-MB-231)、神经母细胞瘤 (SH-SY5Y) 和急性单核细胞白血病 (THP-1) 细胞系的 T 细胞来测试我们方法的普遍性。与对照相比，所得 T 细胞分泌 IFNγ 并发挥增强的肿瘤特异性细胞溶解功能，证明了 PBNP-PTT 在生成用于 ATCT 的肿瘤特异性 T 细胞方面的多功能性。