Recombination Monophosphoryl Lipid A-Derived Vacosome for the Development of Preventive Cancer Vaccines.

Ruoyu Cheng,Flavia Fontana,Jouni T Hirvonen,Mohammad-Ali Shahbazi,Patrícia Figueiredo,Giulia Torrieri,Jing Jin,Wenguo Cui,Zehua Liu,Shiqi Wang,Tongtong Chen,Hongbo Zhang,Hélder A Santos,Yong Lu,Junyuan Xiao

doi:10.1021/acsami.0c15057

Abstract

Recently, there has been an increasing interest for utilizing the host immune system to fight against cancer. Moreover, cancer vaccines, which can stimulate the host immune system to respond to cancer in the long term, are being investigated as a promising approach to induce tumor-specific immunity. In this work, we prepared an effective cancer vaccine (denoted as “vacosome”) by reconstructing the cancer cell membrane, monophosphoryl lipid A as a toll-like receptor 4 agonist, and egg phosphatidylcholine. The vacosome triggered and enhanced bone marrow dendritic cell maturation as well as stimulated the antitumor response against breast cancer 4T1 cells in vitro. Furthermore, an immune memory was established in BALB/c mice after three-time preimmunization with the vacosome. After that, the immunized mice showed inhibited tumor growth and prolonged survival period (longer than 50 days). Overall, our results demonstrate that the vacosome can be a potential candidate for clinical translation as a cancer vaccine.

Highlights

Vaccines have been considered as one of the most effective approaches in controlling infectious diseases
The scientific community proposes to develop cancer vaccines to prevent cancer, which is expected to be similar to the conventional vaccine in the prevention of infectious diseases.[1−4] The basic mechanism behind cancer vaccination relies on the activation of antigen-presenting cells (APCs), such as dendritic cells (DCs) and macrophages, together with processing of the cancer-related antigens provided by the vaccines.[5,6]
Immunization with the vacosome resulted in increased priming of the TEM and reduction in the intratumoral Treg, which improve the antitumor efficiency compared to CM or Monophosphoryl lipid A (MPLA)@Lip alone

Summary

INTRODUCTION

Vaccines have been considered as one of the most effective approaches in controlling infectious diseases. Cancer cell membranes contain plenty of tumor-specific antigens These antigens can be obtained directly from the isolated cell membranes retaining their bioactivity.[20−22] In addition, the easy cell membrane isolation process makes this approach time effective and inexpensive.[4] the cancer cell membrane cannot work as a preventive cancer vaccine by itself because of the limited ability in boosting immune response.[23]. Nanomaterials have been proved to codeliver antigens and adjuvants in the same carriers and induce robust immune responses.[24−28] Liposomes, a Food and Drug Administration (FDA)-approved nanomaterial, present a phospholipid bilayer structure, which is similar to the structure of the cell membrane.[10] In terms of composition, liposomes, MPLA, and cell membrane mainly consist of phospholipid, which makes liposomes as an ideal nanomaterial to develop the potential ability of MPLA and cancer cell membranes as preventive cancer vaccines. Challenge and in prolonging the overall survival was confirmed by analyzing the ratio of CTLs to CD 3+ cells and the ratio of regulatory T cells (Treg) to CD 4+ cells in the tumor area

RESULTS AND DISCUSSION

CONCLUSIONS

■ ACKNOWLEDGMENTS

■ REFERENCES