Enhanced anti-tumor efficacy of electroporation (EP)-mediated DNA vaccine boosted by allogeneic lymphocytes in pre-established tumor models

Sanyuan Shi, Luchen Zhang, Anjie Zheng, Fang Xie, Samuel Kesse, Yang Yang, Jinliang Peng*, Yuhong Xu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Tumor-reactive T cells play a crucial role in anti-tumor responses, but T cells induced by DNA vaccination are time-consuming processes and exhibit limited anti-tumor efficacy. Therefore, we evaluated the anti-tumor effectiveness of reactive T cells elicited by electroporation (EP)-mediated DNA vaccine targeting epidermal growth factor receptor variant III (pEGFRvIII plasmid), in conjunction with adoptive cell therapy (ACT), involving the transfer of lymphocytes from a pEGFRvIII EP-vaccinated healthy donor. Methods: The validation of the established pEGFRvIII plasmid and EGFRvIII-positive cell model was confirmed through immunofluorescence and western blot analysis. Flow cytometry and cytotoxicity assays were performed to evaluate the functionality of antigen-specific reactive T cells induced by EP-mediated pEGFRvIII vaccines, ACT, or their combination. The anti-tumor effectiveness of EP-mediated pEGFRvIII vaccines alone or combined with ACT was evaluated in the B16F10-EGFRvIII tumor model. Results: EP-mediated pEGFRvIII vaccines elicited serum antibodies and a robust cellular immune response in both healthy and tumor-bearing mice. However, this response only marginally inhibited early-stage tumor growth in established tumor models. EP-mediated pEGFRvIII vaccination followed by adoptive transfer of lymphocytes from vaccinated healthy donors led to notable anti-tumor efficacy, attributed to the synergistic action of antigen-specific CD4+ Th1 cells supplemented by ACT and antigen-specific CD8+ T cells elicited by the EP-mediated DNA vaccination. Conclusions: Our preclinical studies results demonstrate an enhanced anti-tumor efficacy of EP-mediated DNA vaccination boosted with adoptively transferred, vaccinated healthy donor-derived allogeneic lymphocytes.

Original languageEnglish
Article number248
JournalCancer Immunology, Immunotherapy
Volume73
Issue number12
DOIs
Publication statusPublished - Dec 2024
Externally publishedYes

Keywords

  • Adoptive cell transfer
  • DNA vaccine
  • Electroporation
  • Epidermal growth factor receptor variant III (EGFRvIII)
  • Tumor burden

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