Adoptive cell therapy with tumor-infiltrating T cells (TILs) has generated exciting clinical trial results for the treatment of unresectable solid tumors. However, solid tumors remain difficult targets for adoptively transferred T cells, due in part to poor migration of TILs to the tumor, physical barriers to infiltration, and active suppression of TILs by the tumor. Furthermore, a highly skilled team is required to obtain tumor tissue, isolate and expand the TILs ex vivo, and reinfuse them into the patient, which drives up costs and limits patient access. Here, we describe a cell-free polymer implant designed to recruit, genetically reprogram and expand host T cells at tumor lesions in situ. Importantly, the scaffold can be fabricated on a large scale and is stable to lyophilization. Using a mouse breast cancer model, we show that the implants quickly and efficiently amass cancer-specific host lymphocytes at the tumor site in quantities sufficient to bring about long-term tumor regression. Given that surgical care is the mainstay of cancer treatment for many patients, this technology could be easily implemented in a clinical setting as an add-on to surgery for solid tumors. Furthermore, the approach could be broadened to recruit and genetically reprogram other therapeutically desirable host cells, such as macrophages, natural killer cells or dendritic cells, potentially boosting the antitumor effectiveness of the implant even more.

中文翻译：

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基于生物材料的支架，用于肿瘤浸润 T 淋巴细胞的直接原位编程

使用肿瘤浸润 T 细胞 (TIL) 的过继细胞疗法在治疗不可切除的实体瘤方面取得了令人兴奋的临床试验结果。然而，实体瘤仍然是过继转移 T 细胞的困难靶标，部分原因是 TIL 向肿瘤的迁移较差、浸润的物理障碍以及肿瘤对 TIL 的主动抑制。此外，需要一支高技能的团队来获取肿瘤组织，离体分离和扩增 TIL，并将其重新注入患者体内，这增加了成本并限制了患者的使用。在这里，我们描述了一种无细胞聚合物植入物，旨在在肿瘤病变处原位招募、基因重编程和扩增宿主 T 细胞。重要的是，该支架可以大规模制造并且对冻干稳定。使用小鼠乳腺癌模型，我们表明植入物可以快速有效地在肿瘤部位聚集癌症特异性宿主淋巴细胞，其数量足以实现肿瘤的长期消退。鉴于手术治疗是许多患者癌症治疗的主要手段，这项技术可以很容易地在临床环境中实施，作为实体瘤手术的补充。此外，该方法可以扩展到招募和基因重编程其他治疗所需的宿主细胞，例如巨噬细胞、自然杀伤细胞或树突状细胞，从而有可能进一步提高植入物的抗肿瘤效果。