School of Chemical Engineering, Sungkyunkwan University (SKKU), Suwon, 16419, Republic of Korea.
Department of Health Sciences and Technology, Samsung Advanced Institute for Health Science and Technology (SAIHST), SKKU, Suwon, 16419, Republic of Korea.
Adv Healthc Mater. 2019 Mar;8(5):e1800571. doi: 10.1002/adhm.201800571. Epub 2019 Jan 25.
Ex vivo manipulation of autologous antigen-presenting cells and their subsequent infusion back into the patient to dictate immune response is one of the promising strategies in cancer immunotherapy. Here, a 3D alginate scaffold embedded with reduced graphene oxide (rGO) is proposed as a vaccine delivery platform for in situ long-term activation of antigen-presenting dendritic cells (DCs). High surface area and hydrophobic surface of the rGO component of the scaffold provide high loading and a very slow release of a loaded antigen, danger signal, and/or chemoattractant from the scaffold. This approach offers long-term bioavailability of the loaded cargo inside the scaffold for manipulation of recruited DCs. After mice are subcutaneously vaccinated with the macroporous alginate graphene scaffold (MAGS) loaded with ovalbumin (OVA) and granulocyte-macrophage colony-stimulating factor (GM-CSF), this scaffold recruits a significantly high number of DCs, which present antigenic information via major histocompatibility complex class I for a long period. Furthermore, an MAGS loaded with OVA, GM-CSF, and CpG promotes production of activated T cells and memory T cells, leading to the suppression of OVA-expressing B16 melanoma tumor growth in a prophylactic vaccination experiment. This study indicates that an MAGS can be a strong candidate for long-term programming and modulating immune cells in vivo.
将自体抗原呈递细胞进行体外操作,并将其回输到患者体内以调节免疫反应,是癌症免疫治疗中很有前途的策略之一。在这里,提出了一种 3D 藻酸盐支架,其中嵌入了还原氧化石墨烯(rGO),作为疫苗传递平台,用于原位长期激活抗原呈递树突状细胞(DCs)。支架的 rGO 成分具有高表面积和疏水性表面,可为支架提供高负载和非常缓慢的加载抗原、危险信号和/或趋化因子的释放。这种方法可在支架内长时间提供加载货物的生物利用度,从而操纵募集的 DCs。在用负载卵清蛋白(OVA)和粒细胞-巨噬细胞集落刺激因子(GM-CSF)的大孔藻酸盐石墨烯支架(MAGS)对小鼠进行皮下接种后,该支架募集了大量的 DCs,这些 DCs 通过主要组织相容性复合物 I 长时间呈递抗原信息。此外,负载 OVA、GM-CSF 和 CpG 的 MAGS 可促进活化 T 细胞和记忆 T 细胞的产生,从而抑制预防性接种实验中表达 OVA 的 B16 黑色素瘤肿瘤的生长。本研究表明,MAGS 可以成为体内长期编程和调节免疫细胞的有力候选物。