Immunomodulatory biomaterial to enhancing T-cell responses to triple negative breast cancer

项目摘要 死于实体瘤的人数远远超过死于造血系统癌症的人数。然而， 实体瘤的免疫疗法远远落后于淋巴瘤。CAR-T细胞疗法和 工程化T细胞已经成为造血系统癌症的革命性方法，但它们的 但是对于实体瘤的潜力还有待实现。重大挑战阻碍了 实体瘤的免疫治疗，包括激活不足和最终耗尽， 效应T细胞;和肿瘤微环境中T细胞效应应答的抑制。在 本提案考虑了这些障碍，并提供了克服这些障碍的生物材料解决方案。 这一提议在促进内源性T细胞对抗实体瘤方面具有重要意义。手术是一 主要的治疗方式为侵袭性和原位肿瘤，但在这个时候，没有具体的 免疫疗法在手术时开始;它们都在几天到几周后开始。我们的建议 对于提供一种早期开始治疗的方法是很重要的，就在初次手术的时候。这里 我们的合成支架SymphNode可以在活检或手术时注射， 招募和激活经历过肿瘤的局部免疫细胞，同时也抑制抑制性细胞 是由肿瘤细胞产生的我们的长期目标是开发这种生物工程，局部注射， “合成淋巴结”用于治疗人类肿瘤。

Project Summary Deaths from solid tumors vastly outnumber deaths from hematopoietic cancers. Yet progress in immunotherapies for solid tumors is well behind those for lymphoma. CAR-T cell therapies and engineered T cells have become revolutionary approaches for hematopoietic cancers, but their potential for solid tumors is yet to be realized. Significant challenges hinder the potential of immune therapies in solid tumors, including insufficient activation and eventual exhaustion of effector T cells; and suppression of T cell effector responses in the tumor microenvironment. In this proposal we consider these hurdles and offer a biomaterial solution that overcomes them. This proposal is significant in facilitating endogenous T cells to fight solid tumors. Surgery is a major treatment modality for both invasive and in situ tumors, but at this time, there are no specific immunotherapies initiated at the time of surgery; they all start days to weeks later. Our proposal is significant for offering a way to start treatments early, right at the time of initial surgery. Here our synthetic scaffold, SymphNode can be injected at the time of biopsy or surgery not to only recruit and active tumor-experienced local immune cells but also to suppress the inhibitory cells created by tumor cells. Our long-term goal is to develop this bioengineered, locally injected, “synthetic lymph node” into a therapy for human tumors.