Development of a Dendritic Cell/Tumor Cell Fusion Cell Membrane Nano-Vaccine for the Treatment of Ovarian Cancer.

Lei Zhang,Ying Chen,Wei Zhao,Jinke Huang,Hualin Song,Fangxuan Li,Jindong Sheng

doi:10.3389/fimmu.2022.828263

Abstract

Ovarian cancer (OC) is a malignant tumor that seriously affects women’s health. In recent years, immunotherapy has shown great potential in tumor treatment. As a major contributor of immunotherapy, dendritic cells (DCs) - based tumor vaccine has been demonstrated to have a positive effect in inducing immune responses in animal experiments. However, the effect of tumor vaccines in clinical trials is not ideal. Therefore, it is urgent to improve the existing tumor vaccines for tumor treatment. Here, we developed a fusion cell membrane (FCM) nano-vaccine FCM-NPs, which is prepared by fusing DCs and OC cells and coating the FCM on the poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) loaded with the immune adjuvant CpG-oligodeoxynucleotide (CpG-ODN). The fusion process promoted the maturation of DCs, thus up-regulating the expression of costimulatory molecule CD80/CD86 and accelerating lymph node homing of DCs. Furthermore, FCM-NPs has both the immunogenicity of tumor cells and the antigen presenting ability of DCs, it can stimulate naive T lymphocytes to produce a large number of tumor-specific cytotoxic CD8+ T lymphocytes. FCM-NPs exhibited strong immuno-activating effect both in vitro and in vivo. By establishing subcutaneous transplanted tumor model, patient-derived xenograft tumor model and abdominal metastatic tumor model, FCM-NPs was proved to have the effect of delaying the growth and inhibiting the metastasis of OC. FCM-NPs is expected to become a new tumor vaccine for the treatment of ovarian cancer.

Highlights

Ovarian cancer (OC) is one of the most common and fatal malignancies, ranking the third in incidence and the first in mortality among gynecological malignancies
Through SDSPAGE, we found that almost all membrane proteins of OC and dendritic cells (DCs) cells could be found in the fusion cell membrane (FCM) (Figure 2C), demonstrating the successful construction of fusion cells (FCs)
FCM-NPs were constructed by fusing the cell membrane of OC and DC cells and coating the fused cell membrane on the surface of poly(lactic-co-glycolic acid) (PLGA) NPs containing vaccine adjuvant CpG ODN

Summary

Introduction

Ovarian cancer (OC) is one of the most common and fatal malignancies, ranking the third in incidence and the first in mortality among gynecological malignancies. Tumor immunotherapy is a novel therapeutic method, which can recognize and kill tumor cells, and inhibit tumor metastasis and recurrence by activating the patients’ own immune system [3]. Tumor vaccines have shown promising therapeutic effect in clinical trials [6, 7]. They have the characteristics of high specificity, convenient preparation and relatively low cost. In 2006, the US Food and Drug Administration (FDA) approved the first tumor vaccine in the world, the prophylactic tumor vaccineCervarix, which reduces the incidence of human cervical cancer [9]. In April 2010, the FDA approved sipuleucel-T (ProvengeTM) for the treatment of advanced prostate cancer, making it the first autologous active immunotherapy drug and the first truly therapeutic tumor vaccine [10]

Methods

Results

Conclusion