Wu Minliang, Xiao Yuai, Huang Jianguo, Wang Yuchong, Zhang Yifan, Xu Jianguo, Dai Haiying, Lv Chuan, Hu Yihui, Chen Bingdi, Fu Qingge, Le Wenjun, Xue Chunyu
Department of Plastic Surgery, Changhai Hospital, Naval Medical University, Shanghai, 200433, China.
Institute for Regenerative Medicine, Shanghai East Hospital, The Institute for Biomedical Engineering & Nano Science, School of Medicine, Tongji University, Shanghai, 200092, China.
J Cancer Res Clin Oncol. 2023 Nov;149(15):13705-13716. doi: 10.1007/s00432-023-05117-y. Epub 2023 Jul 31.
Cancer vaccine (CV) has thrived as a promising tool for cancer prevention and treatment. However, how to maintain the integrity and diversity of individualized vaccine antigens and activate the adaptive immune system is still challenging.
Herein, a preventive and therapeutic vaccine platform for in situ effective multi-model synergistic therapy is developed. In our study, we process B16F10 cells by liquid nitrogen frozen (LNF) to obtain LNF cells, the characterization of LNF cells were conducted. Moreover, the anti-tumor effect and immune activation ability were studied, and the role as a CV were investigated.
The LNF cells preserve intact cellular structure and tumor-associated self-antigen gp100. Moreover, LNF cells have the ability of loading and releasing doxorubicin (DOX). Except for the anti-tumor effect of chemotherapy brought by DOX, the LNF cells can promote the maturation of dendritic cells (DCs) and induce immune response by activating CD4 and CD8 T cells, particularly with the existence of adjuvant, R848. Specifically, the CD8 T cells of mice in LNF-DOX/R848 group are 6 times of that in PBS group in tumor microenvironment, and twice in spleen. Therefore, LNF cells can also be utilized as a CV. Vaccination with LNF/R848 cells effectively suppress the tumor growth in mice by fivefold as compared to the control group.
In this work, we obtain the LNF cells with a simple procedure. The LNF cells not only provides a tumor cells-based multi-modal system for cancer therapy but inspires new insights into future development of individualized CVs strategies. This study processes live B16F10 cells by liquid nitrogen frozen to obtain LNF cells, which preserve cell integrity and homologous targeting ability. The LNF cells can load and deliver drug and can serve as tumor vaccine. Results demonstrated the LNF cells have effective prophylactic ability, and ideal anti-tumor ability with the loaded drug and adjuvant.
癌症疫苗(CV)作为一种有前景的癌症预防和治疗工具已蓬勃发展。然而,如何维持个体化疫苗抗原的完整性和多样性并激活适应性免疫系统仍然具有挑战性。
在此,开发了一种用于原位有效多模式协同治疗的预防性和治疗性疫苗平台。在我们的研究中,我们通过液氮冷冻(LNF)处理B16F10细胞以获得LNF细胞,并对LNF细胞进行了表征。此外,研究了其抗肿瘤作用和免疫激活能力,并研究了其作为癌症疫苗的作用。
LNF细胞保留了完整的细胞结构和肿瘤相关自身抗原gp100。此外,LNF细胞具有加载和释放阿霉素(DOX)的能力。除了DOX带来的化疗抗肿瘤作用外,LNF细胞还可以促进树突状细胞(DCs)的成熟,并通过激活CD4和CD8 T细胞诱导免疫反应,特别是在佐剂R848存在的情况下。具体而言,LNF-DOX/R848组小鼠肿瘤微环境中的CD8 T细胞是PBS组的6倍,脾脏中的是PBS组的两倍。因此,LNF细胞也可作为癌症疫苗。与对照组相比,用LNF/R848细胞接种疫苗可有效抑制小鼠肿瘤生长达五倍之多。
在这项工作中,我们通过简单的程序获得了LNF细胞。LNF细胞不仅为癌症治疗提供了一个基于肿瘤细胞的多模式系统,还为个体化癌症疫苗策略的未来发展提供了新的见解。本研究通过液氮冷冻处理活的B16F10细胞以获得LNF细胞,其保留了细胞完整性和同源靶向能力。LNF细胞可以加载和递送药物,并可作为肿瘤疫苗。结果表明,LNF细胞具有有效的预防能力,以及与加载的药物和佐剂联合时理想的抗肿瘤能力。