具有持续局部免疫调节作用的预防性和治疗性癌症疫苗。
Prophylactic and therapeutic cancer vaccine with continuous localized immunomodulation.
发表日期:2024 Aug 03
作者:
Nikitha Kota, Daniel Davila Gonzalez, Hsuan-Chen Liu, Dixita Viswanath, Robin Vander Pol, Anthony Wood, Nicola Di Trani, Corrine Ying Xuan Chua, Alessandro Grattoni
来源:
Nanomedicine
摘要:
选择性体内免疫细胞操作为癌症疫苗提供了一种有前途的策略。在这种情况下,对特定细胞招募的时空控制以及它们直接暴露于适当的免疫佐剂和抗原是有效癌症疫苗的关键。我们提出了一种名为“NanoLymph”的植入式 3D 打印癌症疫苗平台,该平台能够在皮下部位进行时空控制的免疫细胞招募和操作。 NanoLymph 利用两个储库,每个储库用于连续免疫佐剂释放或抗原呈递,在现场吸引树突状细胞 (DC) 并将其暴露于肿瘤相关抗原。当局部抗原特异性激活时,树突状细胞被动员起来启动全身免疫反应。 NanoLymph 释放粒细胞-巨噬细胞集落刺激因子和 CpG-寡脱氧核苷酸与辐照的全细胞肿瘤裂解物在预防和治疗性疫苗环境中抑制 B16F10 小鼠黑色素瘤的肿瘤生长。总体而言,这项研究将 NanoLymph 展示为一种多功能癌症疫苗开发平台,具有可补充和受控的抗原和免疫佐剂局部释放。版权所有 © 2024 作者。由爱思唯尔公司出版。保留所有权利。
Selective in vivo immune cell manipulation offers a promising strategy for cancer vaccines. In this context, spatiotemporal control over recruitment of specific cells, and their direct exposure to appropriate immunoadjuvants and antigens are key to effective cancer vaccines. We present an implantable 3D-printed cancer vaccine platform called the 'NanoLymph' that enables spatiotemporally-controlled recruitment and manipulation of immune cells in a subcutaneous site. Leveraging two reservoirs each for continuous immunoadjuvant release or antigen presentation, the NanoLymph attracts dendritic cells (DCs) on site and exposes them to tumor-associated antigens. Upon local antigen-specific activation, DCs are mobilized to initiate a systemic immune response. NanoLymph releasing granulocyte-macrophage colony-stimulating factor and CpG-oligodeoxynucleotides with irradiated whole cell tumor lysate inhibited tumor growth of B16F10 murine melanoma in a prophylactic and therapeutic vaccine setting. Overall, this study presents the NanoLymph as a versatile cancer vaccine development platform with replenishable and controlled local release of antigens and immunoadjuvants.Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.