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Personalized Cancer Immunotherapy Boosted by cGAS-STING-Targeted Nanovaccines in Combination With Nutrient Modulation

Wenping Huang1,2,3, Guoliang Cao1, Mixiao Tan1

  • 1CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety CAS Center for Excellence in Nanoscience National Center for Nanoscience and Technology Beijing China.

Exploration (Beijing, China)
|January 1, 2026
PubMed

Insights

Genetically engineered bacteria produce cyclic dinucleotides (STING agonists) for cancer immunotherapy. Personalized nanovaccines (nECTs) enhance immune responses and remodel the tumor microenvironment, showing promise for oncology treatments.

Area of Science:

  • Immunology
  • Oncology
  • Biotechnology

Background:

  • Cyclic dinucleotides activate the STING pathway, crucial for immune responses in cancer immunotherapy.
  • Current limitations include poor stability and delivery of cyclic dinucleotides, hindering their therapeutic use.

Purpose of the Study:

  • To develop a novel nanovaccine (nECTs) using engineered bacteria for enhanced cancer immunotherapy.
  • To evaluate the efficacy of nECTs in stimulating immune responses and remodeling the tumor microenvironment.

Main Methods:

  • Genetically engineered *E. coli* to produce 2'3'-cGAMP intracellularly.
  • Fabricated personalized nanovaccines (nECTs) by combining engineered bacteria with autologous tumor antigens.
  • Assessed nECTs' in vitro effects on dendritic cell activity and antigen cross-presentation via STING signaling.
  • Evaluated nECTs' in vivo efficacy in mouse models, including combination with a fasting-mimicking diet.

Main Results:

  • nECTs effectively stimulated dendritic cell activity and antigen cross-presentation in vitro.
  • In vivo, nECT vaccination promoted effector T cell infiltration and IFN-β-mediated remodeling of the tumor microenvironment.
  • Combining nECTs with a fasting-mimicking diet synergistically enhanced therapeutic efficacy.

Conclusions:

  • Personalized nanovaccines (nECTs) offer a promising strategy for cancer immunotherapy by leveraging engineered bacteria and STING activation.
  • The combination therapy of nECTs and fasting-mimicking diet shows potential for improved precision and effectiveness in oncology.
Keywords:
2'3'‐cGAMPSTINGfasting‐mimicking dietnanovaccinepersonalized cancer immunotherapy

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