Incorporation of CD40 ligand enhances the immunogenicity of tumor‑associated calcium signal transducer 2 virus‑like particles against lung cancer

Xi,Wang; Ke,Dong; Min,Long; Lin,Wang; Jiahui,Zuo; Fang,Lin; Zhaowei,Gao; Zhe,Zhang; Xi,Chen; Huizhong,Zhang

doi:10.3892/ijmm.2018.3570

Incorporation of CD40 ligand enhances the immunogenicity of tumor‑associated calcium signal transducer 2 virus‑like particles against lung cancer

Authors:
- Wang Xi
- Dong Ke
- Long Min
- Wang Lin
- Zuo Jiahui
- Lin Fang
- Gao Zhaowei
- Zhang Zhe
- Chen Xi
- Zhang Huizhong
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Affiliations: Department of Medical Laboratory and Research Center, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710038, P.R. China
Published online on: March 15, 2018 https://doi.org/10.3892/ijmm.2018.3570
Pages: 3671-3679

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Abstract

The cell surface glycoprotein Trop‑2 is overexpressed in various types of cancer, including in lung cancer, and has recently been used as an effective immunotherapeutic target. CD40 ligand (CD40L), a tumor necrosis factor superfamily member, is a promising immune adjuvant. Human immunodeficiency virus (HIV) gag‑based virus‑like particles (VLPs) are highly immunogenic, and foreign antigens can be incorporated onto their membrane envelope for cancer vaccine development. In the present study, a HIV gag‑based VLP strategy and Bac‑to‑Bac system were utilized to construct Trop‑2, CD40L and gag recombinant baculoviruses, which were then used to infect TN5 cells in order to form Trop‑2 VLPs or Trop‑2‑CD40L VLPs. These VLPs were characterized using transmission electron microscopy and western blot analysis methods. VLPs incorporating murine Trop‑2 only or incorporating Trop‑2 and CD40L were used to immunize C57BL/6 mice. Immunized mice demonstrated high humoral and cellular immunity responses, whereas the Trop‑2‑CD40L VLPs led to higher immune responses in comparison with Trop‑2 only VLPs. Immunization with Trop‑2‑CD40L VLPs also reduced tumor growth more effectively compared with Trop‑2 VLPs. Furthermore, Trop‑2‑CD40L VLP immunization increased the survival rate of Lewis tumor‑bearing mice more significantly when compared with Trop‑2 only VLPs. In conclusion, the present study provided a novel vaccine design by combination of a tumor antigen and an immune adjuvant based on a VLP strategy, which may be potentially applied as an alternative immunotherapeutic option in the treatment of lung cancer.

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