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

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.