Antigen-encoding circular single-stranded DNA for cancer vaccine

Area of Science:

• Biotechnology
• Immunology
• Oncology

Background:

• Messenger RNA (mRNA) vaccines show promise in cancer therapy but face challenges with degradation and transient expression.
• Achieving long-term prevention of cancer recurrence and metastasis requires more stable nucleic acid delivery systems.

Purpose of the Study:

• To introduce circular single-stranded DNA (Css DNA) as a novel, long-acting gene expression vector for cancer immunotherapy.
• To evaluate the efficacy of Css DNA-based vaccines in inhibiting tumor growth and recurrence.

Main Methods:

• Engineered Css DNA vectors for robust, long-term gene expression (over 315 days).
• Utilized ovalbumin (OVA)-encoding Css DNA as a model prophylactic vaccine.
• Investigated the combination of OVA-Css DNA with IL-12-encoding Css DNA for enhanced immune response.

Main Results:

• Css DNA demonstrated significantly longer expression and lower immunogenicity compared to conventional plasmids.
• OVA-Css DNA vaccination effectively inhibited tumor growth and recurrence, prolonging survival.
• Combination therapy with IL-12-Css DNA boosted cytotoxic CD8+ T cells and innate immune cell infiltration in tumors.

Conclusions:

• Css DNA serves as a versatile and potent platform for cancer immunotherapy, overcoming limitations of current nucleic acid vaccines.
• Css DNA enables durable antigen expression and potent immune activation for effective tumor suppression.