Abstract:
We recently developed a monocyte-based cellular vaccine platform for cancer treatment. In contrast to the traditional utilization of monocytes as precursors to generate dendritic cells (DC) for vaccination purposes, we find that freshly isolated monocytes with no differentiation process can be loaded with tumor antigens (Ag) and trigger robust antitumor cytotoxic T lymphocyte (CTL) responses. In this chapter, we describe methods to prepare, administer, and evaluate murine Ly-6Chi monocyte-based cellular vaccines for their therapeutic efficacy. This includes procedures for isolation, purity determination, Ag loading, administration of bone marrow (BM)-derived monocytes, as well as methods to determine vaccine efficacy through the examination of Ag-specific CD8+ T cell expansion and antitumor responses in murine melanoma models. As a vaccine platform, undifferentiated monocytes can be easily adapted to different tumor models with a multitude of target antigens. The method described here seeks to facilitate preclinical research of monocyte-based vaccination as a strategy for cancer immunotherapy.
摘要:
我们最近开发了一种用于癌症治疗的基于单核细胞的细胞疫苗平台。与传统的利用单核细胞作为前体以产生用于疫苗接种目的的树突状细胞(DC)相反,我们发现没有分化过程的新鲜分离的单核细胞可以装载肿瘤抗原(Ag),并引发强大的抗肿瘤细胞毒性T淋巴细胞(CTL)反应。在这一章中,我们描述了准备的方法,administrate,并评估鼠Ly-6Chi单核细胞为基础的细胞疫苗的治疗效果。这包括隔离程序,纯度测定,Ag负载量,给予骨髓(BM)衍生的单核细胞,以及通过检测小鼠黑色素瘤模型中Ag特异性CD8+T细胞扩增和抗肿瘤反应来确定疫苗效力的方法。作为疫苗平台,未分化的单核细胞可以容易地适应具有多种靶抗原的不同肿瘤模型。本文描述的方法旨在促进基于单核细胞的疫苗接种作为癌症免疫治疗策略的临床前研究。