2. Academic Validation
  3. Dual-targeting vaccine of FGL1/CAIX exhibits potent anti-tumor activity by activating DC-mediated multi-functional CD8 T cell immunity

Dual-targeting vaccine of FGL1/CAIX exhibits potent anti-tumor activity by activating DC-mediated multi-functional CD8 T cell immunity

  • Mol Ther Oncolytics. 2021 Nov 29:24:1-13. doi: 10.1016/j.omto.2021.11.017.
Dafei Chai 1 2 3,  Dong Qiu 1 4,  Xiaoqing Shi 5,  Jiage Ding 1 2 3,  Nan Jiang 1 4,  Zichun Zhang 1 4,  Jiawei Wang 1 2 3,  Jie Yang 1 2 3,  Pengli Xiao 6,  Gang Wang 1 2 3,  Junnian Zheng 2 3
Affiliations

Affiliations

  • 1 Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China.
  • 2 Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China.
  • 3 Center of Clinical Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
  • 4 Department of Urology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
  • 5 Department of General Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
  • 6 Department of Hematology, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang, Henan, China.
PMID: 34977338 DOI: 10.1016/j.omto.2021.11.017
Abstract

Tumor DNA vaccine as an effective therapeutic approach can induce systemic immunity against malignant tumors, but its therapeutic effect is still not satisfactory in advanced renal Cancer. Herein, a novel DNA vaccine containing dual antigens of fibrinogen-like protein 1 (FGL1) and Carbonic Anhydrase IX (CAIX) was developed and intramuscularly delivered by PLGA/PEI nanoparticles for renal Cancer therapy. Compared with PLGA/PEI-pCAIX immunization, PLGA/PEI-pFGL1/pCAIX co-immunization significantly inhibited the subcutaneous tumor growth and promoted the differentiation and maturation of CD11c+ DCs and CD11c+CD11b+ DCs subset. Likewise, the increased capabilities of CD8 T cell proliferation, CTL responses, and multi-functional CD8+ T cell immune responses were observed in PLGA/PEI-pFGL1/pCAIX vaccine group. Interestingly, depletion of CD8+ T cells by using CD8 mAb resulted in a loss of anti-tumor function of PLGA/PEI-pFGL1/pCAIX vaccine, suggesting that the anti-tumor activity of the vaccine was dependent on CD8+ T cell immune responses. Furthermore, PLGA/PEI-pFGL1/pCAIX co-immunization also suppressed the lung metastasis of tumor mice by enhancing the multi-functional CD8+ T cell responses. Therefore, these results indicate that PLGA/PEI-pFGL1/pCAIX vaccine could provide an effective protective effect for renal Cancer by enhanced DC-mediated multi-functional CD8+ T cell immune responses. This vaccine strategy offers a potential approach for solid or metastatic tumor treatment.

Keywords

CAIX; FGL1; multi-functional CD8+ T cells; renal cancer; therapeutic effects; tumor vaccine.

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