Liquid nitrogen frozen cells for chemotherapy drug delivery and vaccination of melanoma

Minliang Wu; Yuai Xiao; Jianguo Huang; Yuchong Wang; Yifan Zhang; Jianguo Xu; Haiying Dai; Chuan Lv; Yihui Hu; Bingdi Chen; Qingge Fu; Wenjun Le; Chunyu Xue

doi:10.1007/s00432-023-05117-y

Liquid nitrogen frozen cells for chemotherapy drug delivery and vaccination of melanoma

J Cancer Res Clin Oncol. 2023 Nov;149(15):13705-13716. doi: 10.1007/s00432-023-05117-y. Epub 2023 Jul 31.

Authors

Minliang Wu^#¹, Yuai Xiao^#¹, Jianguo Huang^#², Yuchong Wang¹, Yifan Zhang², Jianguo Xu¹, Haiying Dai¹, Chuan Lv¹, Yihui Hu², Bingdi Chen², Qingge Fu³, Wenjun Le⁴, Chunyu Xue⁵

Affiliations

¹ Department of Plastic Surgery, Changhai Hospital, Naval Medical University, Shanghai, 200433, China.
² Institute for Regenerative Medicine, Shanghai East Hospital, The Institute for Biomedical Engineering & Nano Science, School of Medicine, Tongji University, Shanghai, 200092, China.
³ Department of Orthopedic Trauma, Changhai Hospital, Naval Medical University, Shanghai, 200433, China. fqg7821@163.com.
⁴ Institute for Regenerative Medicine, Shanghai East Hospital, The Institute for Biomedical Engineering & Nano Science, School of Medicine, Tongji University, Shanghai, 200092, China. wenjunle@tongji.edu.cn.
⁵ Department of Plastic Surgery, Changhai Hospital, Naval Medical University, Shanghai, 200433, China. xcyfun@sina.com.

^# Contributed equally.

PMID: 37522925
DOI: 10.1007/s00432-023-05117-y

Abstract

Purpose: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Chemotherapy; Drug delivery; Liquid nitrogen frozen; Melanoma; Vaccine.

Abstract

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